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Phase II Trial of Loubo® (Lobaplatin) and Pemetrexed for Patients with Metastatic Breast Cancer not Responding to Anthracycline or Taxanes

  • Deng, Qian-Qian;Huang, Xin-En;Ye, Li-Hong;Lu, Yan-Yan;Liang, Yong;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.413-417
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    • 2013
  • Purpose: This phase II study was undertaken to determine the efficacy and safety of Loubo$^{(R)}$ (Lobaplatin) in combination with pemetrexed in treating patients with metastatic breast cancer who failed to respond to anthracycline or taxanes. Patients and Methods: Metastatic breast cancer cases who had previously received an anthracycline and a taxane in either adjuvant or metastatic settings, were enrolled. All patients were recruited from Jiangsu Cancer Hospital and Research Institute, and were treated with Loubo$^{(R)}$ (Lobaplatin) 35 $mg/m^2$ (intravenous; on day 1) and pemetrexed 500 $mg/m^2$ (intravenous; on day 1) every 21 days. Efficacy and side effects were evaluated after at least two cycles of chemotherapy. Results: All eligible 19 patients completed at least 2 cycles of chemotherapy with pemetrexed and lobaplatin, and were evaluable. Overall, 3 (15.8%) patients achieved partial response, 11 (57.9%) stable disease, 5 (26.3%) progression of disease, with no complete remission. Response rate was 15.8%, disease control rate was 42.1%. The median survival time was 10.3 months. Neutrophil suppression occurred in 36.8% of patients who had grade 2 toxicity, and 26.3% had grade 3, 26.4% had grade 4. Thrombocytopenia was encountered as follows: 21.1% grade 2, 15.8% grade 3 and 5.5% grade 4. Incidences of anemia were 10.5% in grade 2, 5.3% grade 3 and 0% grade 4. Only 5.3% of patients required packed red blood cell transfusion. Grade 3 digestive tract toxicity occurred in 5.5% of patients. Other toxicities included elevated transaminase,oral mucositis and skin rashes. Conclusions: The regimen of lobaplatin and pemetrexed is modestly active in metastatic breast cancer patients who failed anthracycline or taxanes, and the toxicity profile suggesting that the doses of chemotherapy should be further modified.

THe Effects of the Administration on Oriental Medicine, Dalsaengtang, in the Pregnant Rat and Their Fetuses (달생탕이 랫드의 모체와 태자에 미치는 영향에 대한 연구)

  • Park, Hae-Mo;Kim, Chang-Seok;Lee, Sun-Dong;Lee, Jang-Woo;Ryu, Jae-Hong;Kim, Pan-Gyi
    • Journal of Environmental Health Sciences
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    • v.32 no.4 s.91
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    • pp.342-352
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    • 2006
  • The experiments was undertaken to evaluate the effects of herbal medicine, Dalsaengtang, in pregnant rats and fetuses. Female Sprague-Dawley rats were orally administered with the Dalsaengtang at dose of 5 mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weight of dalsaengtang treated group has a tendency to increase compared to that of control group. The relative liver and kidney weights of dalsaengtang treated group were also increased to that of control group. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But Dalsaengtang administered group showed lower early resorption rate than the control group. From the sex ratio, number of females, bigger than number of males in the control group, and more males than females in Dalsaengtang administered group. Neonatal body weight and number of fetus of Dalsaengtang group were increased to that of control group. The fetuses of dams treated with Dalsaengtang didn't showed external malformation. Vertebral and sternal variations were observed in Dalsaengtang group but, compared to the control, those variations were insignificant. The number of ribs, cervical, thoracic, and lumber were normal. The number of sacral and caudal vertebrae were increased. Fetuses showed significant difference in the number of caudal vertebra (P<0.01). From these results, it can be concluded that Dalsaengtang showed no toxicity effects on maternal body weight, early resorption rate, and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. Although skeletal variations were showed in vertebrate and sternum, Dalsaengtang did not shown significant changes in bone malformation.

Effects of Antioxidant Nutrient Supplementation on the Lipid Peroxidation and Antioxidative Enzyme Activities in Patients with Coronary Heart Disease

  • Joung, Hyojee;Chun, Byung Yeol;Choi, Young Sun;Kim, Sueun;Park, Wee Hyun;Jun, Jae Eun;Chae, Shung Chull;Song, Kyung Eun;Cho, Sung Hee;Oh, Hee Sook
    • Preventive Nutrition and Food Science
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    • v.6 no.1
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    • pp.51-56
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    • 2001
  • This study was carried out to evaluate whether antioxidant nutrient suppplementation with $\alpha$-tocopherol, vitamin C, $\beta$-carotene, and selenium reduces the lipid peroxide levels and increases the antioxidative enzyme activities in patients with coronary hart disease. Eighty nine patients participated in a randomized, double-blind, placebo-controlled trial. The antioxidant group (45 patients) was given daily doses of $\alpha$-tocopherol (400 IU), vitamin C (50 mg), $\beta$-carotene (15 mg), and selenium (50 $\mu\textrm{g}$) and forty four patients received a placebo. Thirty eight subjects (84.4%) of the antioxidant group and thirty nine subjects (88.6%) of the placebo group completed the three-month supplementation. Serum levels of tocopherol, vitamin C and $\beta$-carotene significantly increased in the antioxidant group compared with the baseline (p<0.05). Thiobarbituric acid-reactive substances(TBARS) decreased significantly (0.6 nmol MDA/mL) in the antioxidant group compared with that (0.09 nmol MDA/mL) in the placebo group (p=0.03). However, antioxidant supplementation did not affect the level of oxidized-LDL measured as autoantibodies against oxidized-LDL. The superoxide dimutase activity in red blood cells increased in the antioxidant group compared with the baseline (p<0.05). However, glutathione peroxidase activities did not change after supplementation in both groups, and catalase activity significantly decreased in the placebo group (p<0.05). These results suggest that antioxidant supplementation for 3 months with $\alpha$-tocopherol, vitamin C, $\beta$-carotene and selenium in patients with coronary heat disease may be partially protective against oxidative stress.

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Study on the Influenza Type A Activity of Fractions of Korean Medicinal Herbs (한약 단미제 분획의 Influenza virus type A 활성에 관한연구)

  • Jung, Jae-Deuk;Park, In-Ho;Lee, Kwang-Hee;Kim, Ho-Kyoung;Ko, Byung-Seob;Park, Kap-Joo
    • Korean Journal of Oriental Medicine
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    • v.3 no.1
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    • pp.67-83
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    • 1997
  • In order to search for anti-influenza virus type A agents from Korean medicinal herbs, we selected 100 medicinal herbs, based on a review of the Korean traditional medicine books. Four of 100 Korean medicinal herbs, MM-40, MM-55, MM-63, MM-110, exhibited very strong anti-influenza virus activity. The fractions of four medicinal herbs, which had very strong anti-influenza virus activity, were tested for antiviral activity by means of Haemagglutination inhibition test(HTT), 40% MeOH fraction of MM-40, $H_2O$ fraction of MM-55, 20% fraction of MM-63 3nd $H_2O$ fraction of MM-110 had strong anti-influenza virus activity at the range of $78{\mu}g/ml$ to $156{\mu}g/ml$, 1.56mg/ml to 100mg/ml, 6.25mg/ml to 50mg/ml and $48.7{\mu}g/ml$ to $780{\mu}g/ml$, respectively. These results of HIT indicated that fractions of Korean medicinal herbs might inhibit either attachment of virus to cell surface receptor or penetration of virus into cell during the initial stage of infection. In the cytotoxicity of fractions against red blood cells, 40% MeOH fraction of MM-40, 20% fraction of MM-63 and $H_2O$ fraction of MM-110 showed cytotoxicity at the range of $78{\mu}g/ml$ to 10mg/ml, 50mg/ml to 100mg/ml and $195{\mu}g/ml$ to 100mg/ml, respectively, whereas $H_2O$ fraction of MM-55 did not show cytotoxicity. In order to establish influenza virus adapted animal model, influenza virus type A were passaged 3 and 4 times successively in Balb/c mouse. As a result, we had 4 HA unit titers on the 5 days of 3rd passages and 7 days of 4th passages after infection, respectively.

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NAD Glycohydrolase Activity in Patients of Tuberculosis (결핵환자에서 NAD Glycohydrolase Activity에 관한 연구)

  • Seo, Jae-Seok;Lee, Yong-Chul;Rhee, Yang-Keun
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.489-493
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    • 1994
  • Background: Nicotinamide adenine dinucleotide glycohydrolase(NADase) is located on the surface of the cells. It is bound by glycosylphosphatidylinositol(GPI)-linkage, which can be cleaved by bacterial PI-specific phospholipase C(PI-PLC). Recently, it was studied that NADase was increased in infected tuberculosis animal, but absolute NADase is uncertainly increased because of high NADase in Mycobacterium tuberculosis. Therefore, we studied pure NADase activity in red blood cells of normal person and patients of tuberculosis. Method: We evaluated the 19 healthy adults and 16 tuberculosis infected patients, and then, the latter cases were evaluated after 3 months antituberculosis therapy. NADase activity was calculated by scintillated counting of cleaved radioactive [carbonyl-$^3H$] nicotinamide Result: NADase activity was $2021.1{\pm}824.0\;pmol/min/10^6$ erythrocytes in healthy adults vs. $3339.0{\pm}1568.0$ in tuberculosis infected patients, and was $3339.0{\pm}1568.0$ in pretreated patients vs. $2238.6{\pm}1013.1$ in same 3 months treated patients. Conclusion: NADase activity of erythrocytes is elevated in tuberculosis infection, and normalized afer antituberculosis therapy. Therefore, we suggested NADase activity as the new diagnostic and therapeutic indicator.

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Effect of Suoyounsoodan(首烏延壽丹) on Antioxidant Capacity in G-galactose induced Aging Rats (수오연수단(首烏延壽丹)이 노화유발 흰쥐의 항산화능에 미치는 영향)

  • Kwak Byeong-Hoon;Lee Song-Shil;Lee Sang-Jae;Kim Kwang-Ho
    • Journal of Society of Preventive Korean Medicine
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    • v.7 no.1
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    • pp.29-45
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    • 2003
  • Objectives : Suoyounsoodan(首烏延壽丹) composed of Polygonum multiflorum THUNB. and some medical herbs is known as formula of senescence delay effect The purpose of this study is to investigate the effect of Suoyounsoodan(首烏延壽丹) on antioxidant enzyme activity such as Thiobarbituric acid reactive substance(TBARS), Superoxide dismutase(SOD), Catalase(CAT), Glutathione peroxidase(GSH-px) in rat plasma and liver. Methods: Sprague-Dawley rats divided into 4 groups, Young group(8 weeks old, N-8), Aging group(18 weeks old, N-18), pathologically induced aging group(injected D-galactose 50mg/kg, 1time/day for 6 weeks, CON) and Suoyounsoodan(首烏延壽丹) administered group(D-galactose 50mg/kg and Suoyounsoodan extracts 840.0mg/kg 1time/day for 6 weeks, SOY). Rats were sacrificed and TBARS, SOD, CAT, and GSH-px were mesured in rat plasma and liver. Results: Plasma and liver TBARS concentrations of SOY group was sinificantly lower than that of control. Red blood cell(RBC) SOD activities of SOY group was increased(F=3.405, p=0.034, ANOVA test), and RBC catalase activities of all experimental groups were not significantly different. RBC GSH-px activities of SOY group was increased(F=9.261, p=0.0001, ANOVA test). Liver SOD activities of SOY group was higher than that of control(F=3.806, p=0.023, ANOVA test). Liver catalase activities of all experimental groups were not significantly different, and liver GSH-px activity of SOY group was significantly higher than that of control(F=3.572, p=0.029, ANOVA test). Conclusions: According to the above results, It is considered Suoyounsoodan is effective in inhibiting lipid peroxidation and increasing anti oxidative enzyme activities in D-galactose induced aging rat.

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Clinical Features of Symptomatic Meckel's Diverticulum in Children: Comparison of Scintigraphic and Non-scintigraphic Diagnosis

  • Rho, Jung Hee;Kim, Jae Sook;Kim, Sang Yong;Kim, Soon Ki;Choi, Yoon Mi;Kim, Sung Min;Tchah, Hann;Jeon, In Sang;Son, Dong Woo;Ryoo, Eell;Cho, Kang Ho;Choi, Deok Young;Kim, Yoon Mi
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.16 no.1
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    • pp.41-48
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    • 2013
  • Purpose: Meckel's diverticulum (MD) has various clinical manifestations, and diagnosis or selectection of proper diagnostic tools is not easy. This study was conducted in order to assess the clinical differences of MD diagnosed by scintigraphic and non-scintigraphic methods and to find the proper diagnostic tools. Methods: We conducted a retrospective review ofthe clinical, surgical, radiologic, and pathologic findings of 34 children with symptomatic MD, who were admitted to Gachon University Gil Medical Center, Inha University Hospital, and The Catholic University of Korea, Incheon St. Mary's Hospital between January 2000 and December 2012. The patients were evaluated according to scintigraphic (12 cases; group 1) and non-scintigraphic (22 cases; group 2) diagnosis. Results: The male to female ratio was 7.5: 1. The most frequent chief complaint was lower gastrointestinal (GI) bleeding in group 1 and nonspecific abdominal pain in group 2, respectively. The most frequent pre-operative diagnosis was MD in both groups. Red blood cell (RBC) index was significantly lower in group 1. MD was located at 7 cm to 85 cm from the ileocecal valve. Four patients in group 1 had ectopic gastric tissues causing lower GI bleeding. The most frequent treatment modality was diverticulectomy in group 1 and ileal resection in group 2, respectively. Conclusion: To diagnose MD might be delayed unless proper diagnostic tools are considered. It is important to understand indications of scintigraphic and non-scintigraphic methods according to clinical and hematologic features of MD. Scintigraphy would be weighed in patients with anemia as well as GI symptoms.

C-terminal Fusion of EGFP to Pneumolysin from Streptococcus pneumoniae modified its Hemolytic Activity (Streptococcus pneumoniae가 생산하는 pneumolysin의 EGFP 융합으로 인한 용혈활성 변화)

  • Chung, Kyung Tae;Lee, Jae Heon;Jo, Hye Ju
    • Journal of Life Science
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    • v.28 no.1
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    • pp.99-104
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    • 2018
  • Streptococcus pneumoniae is one of the major pathogens in community-acquired diseases, and it contains several factors that promote its pathogenesis, including pneumolysin (PLY). PLY is a member of the cholesterol-dependent cytolysin family, which attacks cholesterol-containing membranes, thereby forming ring-shaped pores. Thus, it is a major key target for vaccines against pneumococcal disease. We cloned the PLY gene from S. pneumoniae D39 and inserted it into the pQE-30 vector. Recombinant PLY (rPLY) was overexpressed in Escherichia coli M15 and purified by $Ni^{2+}$ affinity chromatography. Similarly, a PLY-EGFP fusion gene was produced by inserting the EGFP gene at the 3' end of the PLY gene in the same vector, and the recombinant protein was purified. Sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) showed that both recombinant proteins were purified. rPLY exhibited significant hemolytic activity against 1% human red blood cells (RBCs). Complete hemolysis was obtained at 500 ng/ml, and 50% hemolysis was found with a 240 ng/ml concentration. In contrast, rPLY-EGFP did not show hemolytic activity. However, rPLY-EGFP did bind the RBC membrane, indicating that rPLY-EGFP lost hemolytic activity via EGFP fusion, while retaining its membrane-binding ability. These data suggest that PLY's C terminus is important for its hemolytic activity. Therefore, these two recombinant proteins can be extremely useful for investigating the toxin mechanism of PLY and cell damage during pneumonia.

The Significance of SDF-1α-CXCR4 Axis in in vivo Angiogenic Ability of Human Periodontal Ligament Stem Cells

  • Bae, Yoon-Kyung;Kim, Gee-Hye;Lee, Jae Cheoun;Seo, Byoung-Moo;Joo, Kyeung-Min;Lee, Gene;Nam, Hyun
    • Molecules and Cells
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    • v.40 no.6
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    • pp.386-392
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    • 2017
  • Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like characteristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, ${\alpha}-smooth$ muscle actin, platelet-derived growth factor receptor ${\beta}$, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HUVECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the $SDF-1{\alpha}$ and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel-like structures. In conclusion, we demonstrated the perivascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular diseases.

Diagnostic Value of the Cobalt($^{58}Co$) Excretion Test in Iron Deficiency Anemia (철결핍성빈혈(鐵缺乏性貧血)에서 Cobalt($^{58}Co$)배설율검사(排泄率檢査)의 진단적(診斷的) 가치(價値))

  • Sihn, Hyun-Chung;Hong, Kee-Suck;Cho, Kyung-Sam;Song, In-Kyung;Koh, Chang-Soon;Lee, Mun-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.10 no.1
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    • pp.21-34
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    • 1976
  • The diagnosis of iron deficiency rests upon the correct evaluation of body iron stores. Morphological interpretation of blood film and the red cell indices are not reliable and often absent in mild iron deficiency. Serum iron levels and iron-binding capacity are more sensitive indices of iron deficiency, but they are often normal in iron depletion and mild iron deficiency anemia. They are also subject to many variables which may introduce substantial errors and influenced by many pathologic and physiologic states. Examination of the bone marrow aspirate for stainable iron has been regarded as one of the most sensitive and reliable diagnostic method for detecting iron deficiency, but this also has limitations. Thus, there is still need for a more practical, but sensitive and reliable substitute as a screening test of iron deficiency. Pollack et al. (1965) observed that the intestinal absorption of cobalt was raised in iron-deficient rats and Valberg et al. (1969) found that cobalt absorption was elevated in patients with iron deficiency. A direct correlation was demonstrated between the amounts of radioiron and radiocobalt absorbed. Unlike iron, excess cobalt was excreted by the kidney, the percentage of radioactivity in the urine being directly related to the percentage absorbed from the gastrointestinal tract. Recently a test based on the urinary excretion of an oral dose of $^{57}Co$ has been proposed as a method for detecting iron deficiency. To assess the diagnostic value of urinary cobalt excretion test cobaltous chloride labelled with $1{\mu}Ci\;of\;^{58}Co$ was given by mouth and the percentage of the test dose excreted in the urine was measured by a gamma counter. The mean 24 hour urinary cobalt excretion in control subjects with normal iron stores was 6.1% ($1.9{\sim}15.2%$). Cobalt excretion was markedly increased in patients with iron deficiency and excreted more than 29% of the dose. In contrast, patients with anemia due to causes other than iron deficiency excreted less than 27%. Hence, 24 hour urinary cobalt excretion of 27% or less in a patient with anemia suggets that the primary cause of the anemia is not iron deficiency. A value greater than 27% in an anemic subject suggests that the anemia is caused by iron deficiency. The cobalt excretion test is a simple, sensitive and accurate method for the assessment of body iron stores. It may be particularly valuable in the epidemiological studies of iron deficiency and repeated evaluations of the body iron stores.

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