• Title/Summary/Keyword: CDDP

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CDDP induces conformational changes in BTV ds RNA rather than forming protein-protein and/or protein-RNA crosslink (cis-Diamminedichloroplatinum(II) (CDDP)에 의한 불루텅 바이러스 이중가닥 RNA의 구조변화)

  • Yang, Jai-Myung
    • Applied Biological Chemistry
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    • v.34 no.2
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    • pp.86-93
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    • 1991
  • cis-Diamminedichloroplatinum(II)(CDDP), an antitumor drug, did not generate crosslink between bluetongue virus (BTV) capsid protein at moderate concentration. Cesium chloride density gradient centrifugation study revealed that protein-RNA crosslink was not detectable in CDDP treated BTV. CDDP treated BTV ds RNA showed remarkable change in the migration pattern in polyacrylamide gel electrophoresis. These results suggest that the reduction of BTV core associated transcriptase activity is most likely by the CDDP adduction to the genomic ds RNA rather than by the protein-RNA crosslink and/or protein-protein cross-link.

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Effects of Antioxidant on Reduction of Hindlimb Muscle Atrophy Induced by Cisplatin in Rats (항산화제가 시스플라틴에 의해 유발된 쥐의 뒷다리근 위축 경감에 미치는 영향)

  • Kim, Jin Il;Choe, Myoung-Ae
    • Journal of Korean Academy of Nursing
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    • v.44 no.4
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    • pp.371-380
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    • 2014
  • Purpose: The purpose of this study was to examine the effects of Cu/Zn SOD on reduction of hindlimb muscular atrophy induced by cisplatin in rats. Methods: Forty-two rats were assigned to three groups; control group, Cisplatin (CDDP) group and cisplatin with Cu/Zn SOD (CDDP-SOD) group. At day 35 hindlimb muscles were dissected. Food intake, activity, withdrawal threshold, muscle weight, and Type I, II fiber cross-sectional area (CSA) of dissected muscles were measured. Relative SOD activity and expression of MHC and phosphorylated Akt, ERK were measured after dissection. Results: Muscle weight and Type I, II fiber CSA of hindlimb muscles in the CDDP group were significantly less than the control group. Muscle weight and Type I, II fiber CSA of hindlimb muscles, food intake, activity, and withdrawal thresholds of the CDDP-SOD group were significantly greater than the CDDP group. There were no significant differences in relative SOD activities of hindlimb muscles between the CDDP-SOD and CDDP groups. MHC expression and phosphorylated Akt, ERK of hindlimb muscles in the CDDP-SOD group were significantly greater than the CDDP group. Conclusion: Cu/Zn SOD attenuates hindlimb muscular atrophy induced by cisplatin through increased food intake and activity. Increment of phosphorylated Akt, ERK may relate to attenuation of hindlimb muscular atrophy.

Silymarin Modulates Cisplatin-Induced Oxidative Stress and Hepatotoxicity in Rats

  • Mansour, Heba Hosny;Hafez, Hafez Farouk;Fahmy, Nadia Mohamed
    • BMB Reports
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    • v.39 no.6
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    • pp.656-661
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    • 2006
  • Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP -induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.

cis-Diamminedichloroplatinum (II) (CDDP) Inhibits Bluetongue Virus (BTV) Core Associated Transcriptase Activity (CDDP를 처리한 Bluetongue Virus Core의 전사저해)

  • ;Manning, JaRue S.
    • Korean Journal of Microbiology
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    • v.29 no.1
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    • pp.34-39
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    • 1991
  • The BTV core associated transcriptase activity, assayed by acid precipitable counts, was reduced to an undetectable level after treat the core with .$100{\mu}{\M}$ CDDP. When the RNA transcripts prepared from the CDDP treated BTV core were analysed on agaroseurea gel, it was observed that the band intensity of the large size RNA was reduced while the band intensity of the small size RNA was enhanced. Northern blot analysis showed that much of the small size RNAs appeared to be prematurely terminated transcripts. These results suggest that CDDP adduction to the template RNA blocks chain elongation process of the virion bound transcriptase that is ultimately responsible for the inactivation of BTV infectivity.

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MTA1 Overexpression Induces Cisplatin Resistance Innasopharyngeal Carcinoma by Promoting Cancer Stem Cells Properties

  • Feng, Xiaohua;Zhang, Qianbing;Xia, Songxin;Xia, Bing;Zhang, Yue;Deng, Xubin;Su, Wenmei;Huang, Jianqing
    • Molecules and Cells
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    • v.37 no.9
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    • pp.699-704
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    • 2014
  • Themetastasis-associated gene 1 (MTA1) oncogene hasbeen suggested to be involved in the regulation of cancer progression. However, there is still no direct evidence that MTA1 regulates cisplatin (CDDP) resistance, as well as cancer stem cell properties. In this study, we found that MTA1 was enriched in CNE1/CDDP cells. Knock down of MTA1 in CNE1/CDDP cells reversed CSCs properties and CDDP resistance. However, ectopic expression of MTA1 in CNE1 cells induced CSCs phenotypes and CDDP insensitivity. Interestingly, ectopic overexpression of MTA1-induced CSCs properties and CDDP resistance were reversed in CNE1 cells after inhibition of PI3K/Akt by LY294002. In addition, MTA1 expression and Akt activity in CNE1/CDDP cells was much higher than that in CNE1 cells. These results suggested that MTA1 may play a critical role in promoting CDDP resistance in NPC cells by regulatingcancer stem cell properties via thePI3K/Akt signaling pathway. Our findings suggested that MTA1 may be a potential target for overcoming CDDP resistance in NPC therapy.

Efficacy and Safety Profile of TS-1 or TS-1/CDDP in Patients with Advanced Gastric Cancer (진행성 위암환자에 있어 TS-1 또는 TS-1/CDDP의 항암효과 및 안정성)

  • Ha,, Tae-Kyung;Kwon, Sung-Joon
    • Journal of Gastric Cancer
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    • v.6 no.3
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    • pp.139-145
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    • 2006
  • Purpose: Although several chemotherapy regimens used against advanced gastric cancer (AGC) have been studied extensively in an attempt to further improve the prognosis of patients, to date, no standard chemo-therapeutic regimens have been established. The aim of this study was to determine the anti-tumor efficacy and safety of TS-1 or TS-1 plus cisplatin (CDDP). Material and Methods: We treated 78 patients with AGC either with $80\;mg/m^{2}$ of TS-1 for 28 days, which was followed by a 2-week rest, or with $80\;mg/m^{2}$ of TS-1 for 21 days and $80\;mg/m^{2}$ of CDDP on day 8 every 5 weeks. Results: Tumor response rates in the neoadjuvant chemotherapy group and in the recurrent or post-palliative surgery group were 87.5% and 32.4%, respectively, and they were 28.6% and 48.4%, respectively, in the TS-1 group and the TS-1 plus CDDP group. The survival rates in the recurrent and the post-palliative surgery group were significantly different according to the degree of tumor response (P=0.0016), but the one-year survival rates according to the kinds of regimens (TS-1 or TS-1/CDDP group) were not significantly different. The incidences of grade 3 or 4 adverse effects in the TS-1 and the TS-1/CDDP groups were 14.3% and 36.8%, respectively. Conclusion: The anti-tumor efficacy and safety of TS-1 and TS-1 plus CDDP in Korean patients with AGC seemed to be high with modest adverse effects, thus suggesting the possible use of this regimen as a standard chemotherapy for gastric cancer.

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Cisplatin and Extract of Tissue Cultured Mountain Ginseng-Induced Apoptosis in Human Cervical Cancer Cells (인체 자궁암세포에서 cisplatin과 산삼배양근추출물에 의한 apoptosis유도)

  • Lee, Myeong-Seon
    • Applied Microscopy
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    • v.40 no.3
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    • pp.133-138
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    • 2010
  • Mountain ginseng is a perennial crop rarely found in the deep mountains of Korea. The medicinal effect of the mountain ginseng is well known as a panacea in traditional Chinese medicine for a long time. But scientific studies to elucidate the medicinal effect of the mountain ginseng have never been made on account of lack of sample. Recently an improved method of adventitious root culture system through the use of bioreactor has been developed in Panax ginseng that seems to be a reliable way of commercialization of root derived secondary metabolites. This experiment was conducted to evaluated chemotherapeutic effect against human cervical cancer cells by cisplatin (CDDP) and extract of tissue cultured mountain ginseng (ETCMG). CDDP and ETCMG-induced apoptotic cell death in human cervical cancer cell line, HeLa was confirmed by the analysis of cell growth, morphological changes, DNA fragmentation, flow cytometry showed that ETCMG is an inducer of apoptosis and synergizes with CDDP. These results suggest that ETCMG present evidence of anticancer effect and could have a possibly natural therapeutic potential in cervical cancer patients.

cis-Diamminedichloroplatinum (II) induces denaturation and conformational changes in pBR322 DNA (cis-Diamminedichloroplatinum(II)에 의한 pBR322 DNA의 변성과 구조 변화)

  • Koo, Ja-Choon;Lim, Chang-Soo;Hahn, Tae-Ryong;Yang, Jai-Myung
    • Applied Biological Chemistry
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    • v.33 no.4
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    • pp.343-348
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    • 1990
  • E. coli LE392, transformed with CDDP-treated pBR322 DNA, was plated on ampicillin containing media. The number of colonies formed on ampicillin containing agar plate was reduced to undetectable level after treat the DNA with 13.3 ${\mu}M$ CDDP. The CDDP-treated pBR322 DNA was susceptible to sing1e strand DNA specific S1 nuclease and it's migration Pattern in agarose gel electrophoresis was changed. These results suggest that CDDP adduction to pBR322 DNA resulted in denaturation of the double helix and changes in it's conformation which ultimately leads In the inactivation of the ampicillin resistant sere.

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A Comparison between Effects of Anorexia Induced by Consecutive Low-Dose Cisplatin and High-Dose Cisplatin on Hindlimb Muscles of Rats (시스플라틴에 의해 유발된 식욕부진이 쥐의 뒷다리근에 미치는 영향: 저용량 연속투여요법과 고용량 투여요법 간의 비교)

  • Kim, Jin-Il;Choe, Myoung-Ae
    • Journal of Korean Biological Nursing Science
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    • v.14 no.1
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    • pp.49-56
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    • 2012
  • Purpose: The purpose of this study was to compare the effects of anorexia induced by consecutive low-dose and high-dose of cisplatin (CDDP) on the hindlimb muscles of rats. Methods: Male Sprague-Dawley rats were assigned to three groups: Control group (C) received a saline (the same dose and duration as the low CDDP group), the high-dose cisplatin (High CDDP) group received a single 5 mg/kg dose of cisplatin, the consecutive low-dose cisplatin (Low CDDP) group had 1 mg/kg of cisplatin administered for five consecutive days. On the 8th day the soleus and gastrocnemius muscles were dissected. Body weight, food intake, activity, muscle weight, Type I, II fiber cross-sectional area (CSA) of the dissected muscles were measured. Results: Body weight, food intake, muscle weight and Type I, II fiber CSA of the High CDDP and Low CDDP groups were significantly less than the C group. The High CDDP group showed significant decreases, compared to the Low CDDP group, in body weight, food intake, activity score, muscle weight and Type I, II fiber CSA. Conclusion: Hindlimb muscle atrophy occurs due to anorexia induced by both consecutive low-dose and high-dose cisplatin. The muscle atrophy induced by consecutive low-dose cisplatin is less apparent than high-dose cisplatin.

L-Arginine Ameliorates Kidney Function and Urinary Bladder Sensitivity in Experimentally-induced Renal Dysfunction in Rats

  • Mansour, Mahmoud A.;Al-Shabanah, Othman A.;El-Khashef, Hassan A.
    • BMB Reports
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    • v.36 no.4
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    • pp.373-378
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    • 2003
  • Effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on the renal dysfunction that is induced by cisplatin (CDDP) were investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced renotoxicity, which was manifested by increasing the sensitivity of isolated urinary bladder rings to acetylcholine (ACh), together with a significant elevation of serum urea and creatinine, and a severe decrease in serum albumin. Moreover, renal dysfunction was further confirmed by a significant decrease of enzyme activities, such as glutathione peroxidase, GSH-Px (E.C 1.11.1.9), catalase (E.C 1.11.1.6), as well as a significant increase in lipid peroxides that were measured as malondialdhyde (MDA) in kidney tissue homogenates. The administration of L-arginine (70 mg/kg/d p.o in drinking water 5 d before and 5 d after the CDDP injection) significantly ameliorated the renotoxic effects of CDDP, as judged by restoring the normal responses of isolated bladder rings to Ach, and also by an improvement in a range of renal function indices, which included serum urea and creatinine concentrations and kidney weight. In addition, L-arginine prevents the rise of MDA, as well as a reduction of GSH-Px and catalase activities in kidney tissues homogenates. On the other hand, the administration of L-NAME (4 mg/kg/d p.o) resulted in no protection against renal dysfunction that was induced by CDDP treatment. The findings of this study suggest that L-arginine can attenuate kidney injury that is produced by CDDP treatment. In addition, L-arginine may be a beneficial remedy for CDDP-induced renal toxicity, and could be used to improve the therapeutic index of CDDP.