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Effects of Ibandronate on the Expression of Matrix Metalloproteinases in Human U2OS Osteosarcoma Cells (사람 U2OS 골육종 세포에서 Matrix Metalloproteinase의 발현에 Ibandronate가 미치는 영향)

  • Jung, Sung-Taek;Seo, Hyoung-Yeon;Xin, Zeng-Feng;Kim, Yang-Kyung;Kim, Hyung-Won
    • The Journal of the Korean bone and joint tumor society
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    • v.15 no.2
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    • pp.111-121
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    • 2009
  • Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

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A Clinical Study for Promoting Quality Nusing Care in a University Hospital (질적 간호제공을 위한 간호단위 시범 운영 효과에 관한 임상적 연구)

  • Lee, A.J.;Kim, S.H.;Seong, Y.H.;Yoo, S.A.;Kwon, I.G.;Jeong, Y.I.;Nam, H.K.;Kwon, E.J.
    • The Korean Nurse
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    • v.32 no.5
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    • pp.66-77
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    • 1994
  • The purpose of this study was to develop a new nursing unit which can meet changing health care needs, enhance patients' satisfaction and nurses' job satisfaction, and finally guarantee quality nursing care with present manpower. For this, one medical unit was selected as a unit for quality care. And one medical unit which is similar in staffing and patients' characteristics was selected as a control unit. To assess present problems and identify the remedies to the problems a hospital-wide survey and a workshop were performed. According to the survey results, educational programs and improvement of the facilities and equipment supply system, managereal support for interdepartmental cooperation and intensification of bed-side nursing care were adopted as main principles for operating model unit, This model unit was operated for 3 months from Sep. 1, 1992 to Nov. 30, 1992. To evaluate the effectiveness of the model unit, derect/indirect nursing care hours, patients' satisfaction to nursing care, nurses' job satisfaction, and quality care index were measured. Direct/indirect nursing care hours were compared with that of the control unit, and patients' and nurses' satisfaction and quality care index were measured before and after operating model unit and compared with each other. The results of the study were as follows; 1. In the model unit mean direct nursing care hours per cach shift was 146.88 minutes and indirect nursing care hours was 354.72 minutes. The ratio of the direct nursing care hour to indirect nursing hour was 29.6 ; 70.4 and that of the control unit was 26.9 : 73.1. Direct nursing care hour in model unit was longer than that of the control unit. But, the difference was not significant. In subcategories of direct nursing care, the time spent in mobility and exercise, conservation of body temperature, hygiene, and communication and health education were longer than that of the con" trol unit. 2. Indirect nursing care hour in model unit was shorter than that of the control unit. But, the difference was not significant. In subcategories of indirect nursing care, the time spent in drug management and ward arrangement was shorter than that of the control unit. 3. Patients' satisfaction to nursing care was increased significantly after operating the model unit (T=-3.48, P=-0.002) and satisfaction to subcategories of physical comfort measure, psychological cate, and unit management components were significantly higher than before. 4. In the model unit, nurses' total job satisfaction was increased significantly after operating the model unit(Z=2.1004, P=.0357) and satisfaction to subcategory of satisfaction to administration was significantly higher than before (Z=-2.0732, P=.0382). 5. After operating the model unit, quality care index was increased from 89 to 93. With this results, it can be summarized that all the measures tried for quality care, such as educational programs, managereal support for interdepartmental cooperation, and improvement of the equipment and facility provision resulted in partial increase in direct nursing care hours, nurses satisfaction to their job and patients' satisfaction to nursing care. In can be postulated that managereal support and motivation without proper staff supplementation is not enough for increasing direct nursing care hours. And for the enhancement of the level in clinical nursing, and staff supplement must be considered sincerely and the measures for reducing indirect nursing care hours, such as computerization of nursing care activities, improvement of facilities and equipment and facilities supply system, must be instituted in addition.

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A Study on Implementation of Primary Health Care Delivery System meet to Rural Area in Korea -Village Health Voluntary Worker Development- (우리 나라 농촌지역(農村地域)에 부합하는 1차(次) 보건의료전달체계(保健醫療傳達體系) 정착구현(定着具現)에 관한 연구(硏究) -마을 보건임원(保健任員) 개발(開發)-)

  • Koo, Y.C.;Wie, J.H.;Hwang, S.J.;Choi, S.S.
    • Journal of Preventive Medicine and Public Health
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    • v.12 no.1
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    • pp.13-23
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    • 1979
  • A study was carried out from October 1977 to September 1978 in order to develope health care delively system which will meet to rural area in Korea. For the study objective a model of health care delivery system of Myun (township) area was developed which is adopted the net-work of village health voluntary worker who will play the role of bridge for communication related with health and illness between families or village people and health subcenter, and :he model health care delivery system net-work was set in the area of Soodong Myun, Yangju Gun. which is the rural health demonstration area of Ewha Womans University since 1972. The activities and attitude of 22 village health voluntary workers were observed and analized. during the study period. The results are as follows; 1. For the field activities of village health voluntary workers. a guide line which is described with specific behavioral objectives was developed and used for not only training of the workers but also evaluation of their field activities. 2. During the study period, the number of 971 village people were served primary health care service by village health voluntary worker and the service was classified largely into symptomatic medications (92%) and preventive measures (8%). 3. Comparative percentage of the number of 894 symptomatic cases cared by village health voluntary workers to 5,695 cases of patient treated by Soodong Health Subcenter during the same period was 15.7%. 4. Annual utility rate of village health voluntary worker by Myun total people was 16.1% but utility rate by Rie was varied from 38.2% to 2.8% which shown there were considerable differences in each Rie. In order to settle the village health care service, the obstructive factors of utility should be detected and their counter measure must be taken. 5. As the health need of village people increases, it is expected that the supplement of drug excluding present sit basic drugs is inevitable, but considering the ability of village health voluntary worker, the selection of additional drugs and education, plan should be carefully studied. 6. It is desirable that a financial resource for supplementary purchase of first aid kit, drugs and materials whould be alloted from village public fund like Saemaeul Women's Club fund, which has already practiced in a few villages in the study area. 7. As pointed out by village health voluntary workers, in order to improve the village health, village leaders should be in the center of it and the cooperation of whole village people is a core of healthful village development, and it is reasonable that the health subcenter backs up these voluntary health activities by village people in techniques. 8. It seems effective that a supplementary education for village health voluntary worker be accomplished by a planned education through regular meetings like worker's monthly meeting and irregular post guide when Myun Health Workers can handle the problems found during the round trip of villages. 9. It is desirable that village health voluntary workers, who are recommended by a civil voluntary organization like Saemael Woman's Club, are charged by natural villagc unit, are given a function of village health care service and used through basic education at health subcenter. 10. It is advisable that the village health voluntary worker's service is compensated not by a form of money, but by other way such as an exemption of medical fee of worker herself or her families in health subcenter can be one method. 11. Daily health activities of each village health voluntary worker should be reported to health subcenter by biweekly or monthly in order to get not only for basic data of the program but also for evaluation the program. It is recomandable that the report form should be simple and clear enough for village health voluntary worker to fill it effectively. 12. Village health care service should be developed into a Saemaeul Movement in which village people actively participate. For this, the appointed function of village health voluntary worker should be absorbed into those of living Environment Betterment Section or Family Planning Section of Saemaeul Women's Club or it is desirable that establish a new section, Village Health Promoting Section and make it involve the appointed functions of those sections mentioned above.

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The Effects of Majarol on the Blood Pressure and Heart Rate in Rats and Isolated Frog Heart (Majarine 유도체인 majarol의 흰쥐에 있어서 혈압 및 심박동수에 대한 작용과 적출 개구리 심장에 대한 작용)

  • Lee Jong-Hwoa;Park Young-Hyun;Cho Byung-Heon;Kim Yu-Jae;Kim Jong-Bae;Kim Chun-Sook;Cha Young-Deog;Kim Young-Suk
    • The Korean Journal of Pharmacology
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    • v.22 no.1 s.38
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    • pp.34-44
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    • 1986
  • In our previous studies, we had clarified many pharmacological effects of majarine: the bacteriostatic effect in vitro; the potentiation of hypnotic action of alcohol; hypotensive effect in rats and hypothermic effect in mice. This study was undertaken to search for a new antihypertensive drug. Red crystalline was obtained from majarine (which was extracted from Berberis koreana Palibin) by chemical methods. And this crystalline was identified as $C_{19}H_{16}NO_4$ contained one hydroxy group instead of methoxy group of majarine in isoquinoline ring and named 'Majarol' (5,6-Dihydro-9-hydroxy, 10-methoxybenzo-[g]-1,3-benzodioxolo [5,6-a] quinolizinium). We examined the effects of majarol on blood pressure and heart rate in urethane ancsthetized rats and the rate and amplitude of contraction of isolated frog heart. Several drugs: atropine sulfate, diphenhydramine chloride, hexamethonium bromide, phentolamine, epinephrine, propranolol and isoproterenol were used to clarify the mechanism of the hypotensive action of majarol. The results of experimints were as follows; 1. In low dose (0.5-2mg/kg, i.v.), majarol showed a typical transient hypotensive effect and slight decrease in heart rate. In high dose (5-10 mg/kg, i.v.), majarol showed a typical transient and a subsequent prolonged hypotensive effect and a significant prolonged decrease in heart rate was followed. 2. The hypotensive effects of majarol was not abolished by the pretreatments with atropine sulfate, hexamethonium bromide and diphenhydramine. The pretreatment with phentolamine inhibited significantly the hypotensive effects of majarol and the pretreatment wtih majarol blocked markedly the hypertensive effect of epinephrine. The positive chronotropic effect of isoproterenol was not blocked by the pretreatment with majarol. 3. In low dose, majarol increased the amplitude and decreased rate of contraction, but in high dose, majarol inhibited the amplitude and rate of contraction of isolated frog heart.

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Studies on the Fracture Healing in the Alloxan treated Rabbits (Alloxan 투여 가토(家兎)에 대한 골절치유 실험)

  • Kim, Sung-Joon
    • The Korean Journal of Pharmacology
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    • v.7 no.1
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    • pp.53-65
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    • 1971
  • It is well known that diabetes mellitus is associated with metabolic derangements, such as hyper-glycemia, ketosis, glycosuria, and also widespread alterations in the blood vessels, kidneys, eyes, peripheral nerves and heart. It is also recognized that healing of skin wound is delayed in diabetics. In bone, according to Aegerter, osteopenia develops in diabetes mellitus and it is chiefly ascribed to overutilization of protein. Shim claims that total blood flow to the entire skeletal system is approximately 4 to 8 percent of resting cardiac output and blood supply to the skeletal system would be decreased on account of secondary arteriosclerotic changes in the diabetics. An adequate blood supply is an essential factor in the healing process of fracture, and disturbed blood flow, either local or systemic, will invariably delay union of the fragments or the fragments from being fused. As the author has encountered several cases of diabetics in whom healing of fracture was delayed or incomplete, this experimental study was undertaken to elucidate the effects of hyperglycemia and diabetes mellitus on the healing process of fracture. In this experiment adult albino rabbits, weighing about 2 kg. were used and divided into 6 groups. The femur of each animal was fractured surgically, and then the healing process of fracture was periodically checked by radiography at an interval of one week for a period of 6 weeks. Thereafter, all the rabbits were killed to obtain tissue preparation of the femur. The experimental groups were as follows; 1) Control group: Six rabbits sustained a surgical fracture to the femur, without being given any other treatment or drug. 2) Alloxan-treated group: For inducing diabetes, alloxan was given intravenously to 17 rabbits in various dose as follows; to 7 of them 40 mg/kg, to 6 rabbits 80 mg/kg and to 4 rabbits 120 mg/kg of body weight, respectively. 3) Insulin-treated group: Protamine-zinc insulin was injected subcutaneously to each of 6 rabbits in a daily dose of 1 unit per kilogram of body weight. 4) Group treated with insulin after alloxan: Four rabbits were given 80 mg of alloxan once and than 1 unit of insulin per kilogram of body weight daily. Another 5 rabbits were injected 1 unit of insulin per kg of body weight daily following administration of alloxan in a dose of 120 mg/kg. 5) Homotransplantation group: Following intravenous injection of alloxan in a dose of 120 mg/kg, 10 rabbits underwent homotransplantation of a short bone segment to the femur. Five of them were subsequently given 1 unit/kg of insulin daily. 6) Sugar-treated group: six rabbits were fed $15{\sim}20$ gm of sugar daily throughout the period of experiment. The results obtained are summarized as follows; 1. Blood sugar level and damage to the pancreatic islet increased proportionately when alloxan was given to the rabbits in various doses. No appreciable change could be observed in the islets when the blood sugar level was altered by either oral administration of sugar or subcutaneous injection of insulin. 2. Comparing with the control group, healing of fracture was delayed in the alloxan-treated group, while callus formation and periosteal reaction were shown to be more prominent in this group and subsequently, the ultimate osseous tissue formed at the fracture site was significantly smaller in amount and less compact. These findings were more marked as the amount of alloxan increased. 3. Administration of insulin prevented the delay in healing process of fracture in the rabbits with alloxan-induced hyperglycemia. In this case, the course and progression of fracture healing were almost similar to those of control group. 4. Union between the host bone and the fragment transplanted from other rabbit of the same species was more delayed in the group treated with alloxan alone than in the group to which insulin was administered after development of alloxan-induced diabetes. In both groups periosteal new bone developed from the ends of the host bone, above and below the transplanted fragment, and directly fused with failure of periosteal callus to bridge the adjacent ends of the host bone and the transplanted fragment. 5. The healing process of fracture was not inhibited by alteration in blood sugar level when the blood sugar was abnormally increased by excessive sugar intake or lowered by administration of insulin alone. The healing of fracture in these groups progressed similarly as in the control group. In brief summary, it appears that the healing process of fracture would be definitely disturbed in diabetic state brought about by damage to the pancreatic islet. As such an inhibition could be overcome with insulin, it seems that insulin plays an important role in healing of fracture, but alteration in blood sugar level alone does not modify healing process of fracture to significant degree.

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Effect of $Ca^{2+}$ and $Ca^{2+}-antagonists$ on the Spontaneous Contractions and Electrical Activities of Guinea-pig Stomach (기니피그 위 평활근의 자발적 수축과 전기적 활동에 대한 $Ca^{2+}$$Ca^{2+}$-길항제 영향)

  • Rhie, Sang-Ho;Kim, Ki-Whan
    • The Korean Journal of Physiology
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    • v.21 no.2
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    • pp.241-257
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    • 1987
  • The effects of external $Ca^{2+}$ and $Ca^{2+}-antagonists$ on the spontaneous contractions and electrical activities were investigated in guinea-pig stomach in order to clarify the mechanism for the generation of slow waves. Electrical responses of circular smooth muscle cells were recorded using glass capillary microelectrodes filled with 3 M KCl. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The amplitude of spontaneous contractions was maximal at around 2-4 mM $Ca^{2+}$, whereas their frequency was inversely related with external $Ca^{2+}$ within the range of 0.5 to 16 mM $Ca^{2+}$. 2) Verapamil suppressed the amplitude of spontaneous contraction in a dose-dependent manner, while the frequency of spontaneous contractions was almost not changed over the whole concentration of verapamil $(0.01{\sim}5\;mg/l)$. 3) Manganese increased both the amplitude and the frequency of spontaneous contractions dose-dependently in low $Mn^{2+}$ (below 0.05 mM $Mn^{2+}$), while their amplitude and frequency were decreased in high $Mn^{2+}$ (above 0.1 mM $Mn^{2+}$). 4) The ampltude and maximum rate of rise of slow waves were incrased in high $Ca^{2+}$ solution. In $Ca^{2+}-free$ solution, the spontaneous contractions recorded simultaneously with slow waves ceased and tonic contraction ($Ca^{2+}-free$ contracture) was developed in parallel with membrane depolarization and the disappearance of slow waves. 5) Verapamil (1 mg/1) decreased the amplitude and maximum rate of rise of slow waves and it depolarized the membrane by about 6 mV, whereas the frequency of slow waves was not affected by verapamil. 6) Manganese showed different characteristic effects between low and high $Mn^{2+}$ on the slow waves: In low $Mn^{2+}$ (0.05 mM $Mn^{2+}$), the initial rapid increases and the subsequent gradual decreases in three parameters of slow waves (amplitude, rate of rise, and frequency of slow waves) till a new steady state were observed. However, in high $Mn^{2+}$ (0.5 mM $Mn^{2+}$) slow waves disappeared and membrane was depolarized. From the above results, the following conclusions could be made: 1) $Ca^{2+}$ is necessary for a generation of the slow waves, even though it is small amount. 2) Verapamil suppresses the spontaneous contractions of gastric antral strip by the decreases in amplitude and maximum rate of rise of slow waves, while this drug does not block the $Ca^{2+}-channel$ involved in the generation of slow waves. 3) Manganese has dual actions on the $Ca^{2+}-channels$; the $Ca^{2+}-channel$ involved in the generation of slow waves (or Na-Ca exchange system) or the channel for the generation of spike potentials are stimulated by a low concentration of $Mn^{2+}$, while both the $Ca^{2+}$. Channels are blocked by high concentration of $Mn^{2+}$.

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The Effect of 3-(4-hydroxyl -33,53-dimethoxyphenyl)propionic Acid in Chinese Cabbage Kimchi on Lowering Hypercholesterolemia (배추김치의 활성성분인 3-(4-hydroxyl-33,53-dimethoxyphenyl)propionic acid의 고지혈증 치료 효과)

  • 김현주;권명자;서정민;김재곤;송수희;서홍석;송영옥
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.1
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    • pp.52-58
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    • 2004
  • The active principle responsible for lipid lowering in Chinese cabbage kimchi, 3-(4-hydroxyl-3'5'-dimethoxyphenyl)propionic acid, of molecular weight 226, was chemically synthesized and then used for the treatment of hypercholesterolemia in male New Zealand white rabbit. Hypercholesterolemia in rabbits were induced by feeding 0.5% cholesterol added chow diet for 5 weeks. Each experimental group has four rabbits in it. for the 1st experiment,3-(4-hydroxyl-3'5'-dimethoxyphenyl)propionic acid or simvastatin was injected to the ear vein of rabbit every other day for 16 days (2 mg/3 kg/2 days) while normal chow diet was provided. Blood was drawn every 4th day. For the 2nd experiment, all the experimental condition was same as the 1st trial except 0.5% cholesterol diet was provided while 16 days. Plasma cholesterol level was decreased when cholesterol in the diet was removed. Decreased in cholesterol in kimchi and simvastatin groups were 18.65 and 29.67%, respectively compared to the control when the normal diet was given, and cholesterol increase was inhibited by 33.79 and 21.81% for kimchi and simvastatin groups, respectively, when 0.5% cholesterol diet was provided. The drop in LDL-C level by the active principle of kimchi and simvastatin was not significant when normal diet was given, however the changes was significant (p<0.05), approximately 130% decrease, when 0.5% cholesterol diet was given. The 105% and 62% decreased in triglyceride concentration were observed from 0.5% cholesterol diet fed kimchi and simvastatin groups respectively HDL cholesterol levels in experimental groups were not changed significantly from the both trials. The HMG-CoA reductase activity of kimchi and simvastatin groups were found to be higher than that of control to compensate the hypercholesterolemic condition induced by 0.5% cholesterol diet in these groups. In conclusion, diet is an important factor to control the hypercholesterolemia besides drug treatment. 3-(4-hydroxyl-3'5'-dimethoxyphenyl)propionic acid that is the active principle in Chinese cabbage kimchi seems a beneficial to the hypercholesterolemia and its effect is comparable to that of simvastatin.

The Effect of Pleurodesis with Doxycycline in the Rabbit (토끼에서 Doxycycline을 이용한 흉막유착 효과)

  • Won, Kyoung-Sook;Park, Keon-Uk;Jeon, Won-Ho;Baik, Jae-Jung;Jeong, Yeon-Tae;Suh, Jung-Il;Son, Jin-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.531-536
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    • 1994
  • Background: The intrapleural instillation of tetracycline for pleural sclerosis had been most commonly used in patients with symptomatic malignant pleural effusion or recurrent pneumothorax for a long time. Unfortunately, at a time of expanding use of this agent, the production of injectable tetracycline hydrochloride used for pleurodesis was discontinued by its sole manufacturer in mid-1991 because the manufacturer was unable to meet US Food and Drug Administration purity standards. So we performed a preliminary study of doxycycline, as a alternative pleural sclerosant on rabbit pleura and compared its efficacy with that of tetracycline. Method: Eighteen New Zealand white rabbits weighing 2 to 3kg(mean 2.6kg) were devided into three groups. In each groups, one tetracycline(20 mg/ml/kg) and two doxycycline solutions(7 mg/ml/kg and 20 mg/ml/kg) instillated into the right pleural space through an 18-gauge angiocath with care to prevent pneumothorax. All rabbits were sacrificed after 28 days. Results: 1) In the group of tetracycline 20 mg/ml/kg(six rabbits), five rabbits showed partial pleural symphysis with several fibrous bands, and one rabbit died on 22th day. 2) In the group of doxycycline 7 mg/ml/kg(six rabbits), three rabbits showed partial pleural symphysis and the other three rabbits showed complete pleural symphysis without necrosis of underlying parenchymal lung tissue. 3) In the group of doxycycline 20 mg/ml/kg(six rabbits), two rabbits showed complete pleural symphysis without lung necrosis, another two rabbits showed complete pleural symphysis with lung necrosis, and the other two rabbits died on 4th and 13th day, respectively. Conclusion: We concluded that doxycycline is a highly effective sclerosing agent having stronger pleurodesis effect with that of tetracycline by dose base and its optimal dosage was considered as 7 mg/ml/kg with minimal complications.

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The Effect of $I{\kappa}B{\alpha}$-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplatin and Paclitaxel ($I{\kappa}B{\alpha}$-SR 유전자이입이 Cisplatin, Paclitaxel에 대한 폐암세포주의 감수성에 미치는 영향)

  • Lee, Seok-Young;Seol, Ja-Young;Park, Kyung-Ho;Park, Gun-Min;Hwang, Yong-Il;Kim, Cheol-Hyeon;Jang, Seung-Hun;Kwon, Sung-Youn;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.2
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    • pp.122-134
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    • 2001
  • Background : Some chemotherapeutic drugs induce NF-${\kappa}B$ activation by degrading the $I{\kappa}B{\alpha}$ protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting $I{\kappa}B{\alpha}$ degradation would block NF-${\kappa}B$ activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF-${\kappa}B$ inhibitor was transferred by an adenoviral vector (Ad-$I{\kappa}B{\alpha}$-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that $I{\kappa}B{\alpha}$-SR effectively blocked the NF-${\kappa}B$ activation induced by cisplatin. Transduction with Ad-$I{\kappa}B{\alpha}$-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of $IC_{50}$. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF-${\kappa}B$ activation by inducing Ad-$I{\kappa}B{\alpha}$-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of $I{\kappa}B{\alpha}$-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

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Review of Anti-Leukemia Effects from Medicinal Plants (항 백혈병작용에 관련된 천연물의 자료조사)

  • Pae Hyun Ock;Lim Chang Kyung;Jang Seon Il;Han Dong Min;An Won Gun;Yoon Yoo Sik;Chon Byung Hun;Kim Won Sin;Yun Young Gab
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.3
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    • pp.605-610
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    • 2003
  • According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.