• Title/Summary/Keyword: CDDP

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Gallic Acid Hindered Lung Cancer Progression by Inducing Cell Cycle Arrest and Apoptosis in A549 Lung Cancer Cells via PI3K/Akt Pathway

  • Ko, Eul-Bee;Jang, Yin-Gi;Kim, Cho-Won;Go, Ryeo-Eun;Lee, Hong Kyu;Choi, Kyung-Chul
    • Biomolecules & Therapeutics
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    • v.30 no.2
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    • pp.151-161
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    • 2022
  • This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

In Vitro Cytotoxicity of a Novel Platinum(II) Coordination Complex Containing Diaminocyclohexane and Dichloropropane

  • Rho, Young-Soo;Chang, Sung-Goo;Lee, Woo-Tae;Jung, Jee-Chang
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.4
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    • pp.359-366
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    • 2001
  • We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,3-dichloropropane (DCP) as a leaving group. A new series of [Pt(cis- DACH)(DCP)](PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. The new platinum complex has demonstrated high efficacy in the cytotoxicity against MKN-45/P, MKN-45/ADM and MKN-45/CDDP cell-lines. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined by MTT assay, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new, clinically available anticancer chemotherapeutic agents.

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Surgery and Postoperative Immunochemotherapy for Thoracic Esophageal Cancer (흉부식도암의 수술 면역화학요법)

  • 김광택
    • Journal of Chest Surgery
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    • v.26 no.3
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    • pp.214-218
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    • 1993
  • Extensive lymphnode dissection combined with thoracic esophagectomy improved prognosis of esophageal cancer, but there is still high postoperative recurrence rate. The immunologic capacity of esophageal cancer patients is compromised by surgery and adjuvant chemotherapy. Therefore immunological therapy for esophageal cancer patients seems rational. We have adopted postoperative immunochemotherapy since 1988. From 1988 to 1992, 31 patients with thoracic esophageal cancer underwent esophagectomy and radical lymphnode dissection, and selected patient with early esophageal cancer and unfit for thoracotomy underwent transhiatal esophagectomy in Korea University Hospital. Mean age of patients was 56 years. There were 28 squamous cell cancers, 2 adenocarcinomas and one mixed tumor. There were 4 stage I, 3 stage II, 18 stage III, and 6 stage IV cases. There were no opeartive death. Postoperative complications included anastomotic leakage in 9%, pneumonia 3 %, cylothorax 3%, recurrent laryngeal neve paresis in 3% of all patients. Curative resection group[n=19] received immunotherapy. Noncurative resection group[n=12] received postoperative immunochemotherapy, including PS-K, CDDP, and 5-FU. Operative survivors were followed from 4 months to 5 years. There were 3 lost of follow-up. Actuarial survival rate is 79% to one year, 54% to two years and 27% to five years.In conclusion, an transthoracic esophagectomy combined with systematic lymph node dissection and postoperative immunochemotherapy could improve survival rate for esophageal cancer.

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In Vitro Cytotoxicity of a Novel Platinum(II) Coordination Complex Containing Diaminocyclohexane

  • Jung, Jee-Chang;Kim, Soon-Ae;Kim, Young-Kyu;Chang, Sung-Goo;Rho, Young-Soo
    • Biomolecules & Therapeutics
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    • v.8 no.3
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    • pp.228-234
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    • 2000
  • We have synthesized a novel platinum(II) coordination complex containing trans-ι-1,2-diaminocy-clohexane (DACH) as a carrier ligand and 1,2-dichloroethane (DCE) as a leaving group. A new series of [Pt(trans-ι-DACH)(DCE)](PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocar-cinoma cells and normal primary cultured kidney cells. The new platinum complex has demonstrated high efficacy in the cytotoxicity against MKN-45/P, MKN-45/ADM and MKN-45/CDDP cell-lines. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined by MTT assay, the [$^3H$]-thymidine uptake arid glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new, clinically available anticancer chemotherapeutic agents.

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The Design, Implementation and Verification of Distributed Pair Programming System for Supporting Collaboration (협업을 지원하는 분산 페어 프로그래밍 시스템 설계/구현 및 검증)

  • Noh, Hyo-Won;Park, Jin-Ho;Gwak, Hoon-Sung
    • Journal of Advanced Navigation Technology
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    • v.17 no.3
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    • pp.346-353
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    • 2013
  • The dominant trend in software development is the globalisation of the software industry. This development is faced with diverse problems, which require solution by the adoption of new processes and development techniques. eXtreme Programming (known as XP) is one methodology which is now at the leading edge of software development. This recent trend in XP allows organisation members to cooperate towards the development of new software independently of the existing developers. This is achieved functionally between the members by the development of distributed pair programming, this is not IDE plug-in shape of text, simple screen sharing or chatting function based.

Selective Cytotoxicity of Pt (II) Complex Containing 1,2-Bis (diphenylphosphino)ethane on Human Gastric Cancer Cell-Lines and Normal Kidney Cells (1,2-비스 (디페닐포스피노)에탄을 배위자로 한 항암성백금 (II) 착체의 위암세포와 정상신장세포에 대한 선택적 세포독성)

  • 노영수;장성구;정지창
    • YAKHAK HOEJI
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    • v.44 no.5
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    • pp.399-405
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    • 2000
  • We have synthesized a novel platinum (II) coordination complex containing trans-ι-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis (diphenylphosphino)ethane (DPPE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt (trans-ι-DACH) (DPPE)].2NO$_3$(PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against MKN-45/S, MKN-45/ADR and MKN-45/CDDP cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells, and human renal cortical tissues, determined using the MTT assaying technique, the ($^3$H)-thymidine uptake and the glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum (II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

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Attenuation of ROS Generation by KCNE1 Genes in Cisplatin-treated Auditory Cells

  • Kim, Eun Sook;Park, Sang-Ho;Park, Raekil
    • Korean Journal of Clinical Laboratory Science
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    • v.45 no.3
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    • pp.114-119
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    • 2013
  • Potassium is essential for the proper functioning of the ears. The inner ear's endolymph differs from all other extracellular fluids (in its positive potential) and in the ionic compositions in the various parts of the endolymphatic space. Ion concentration of the endolymph is 150 mM of potassium, which is comparable to the concentrations in other organs. Cisplatin (cis-diamminedichloroplatinum II: CDDP) is one of the most effective anticancer drugs, widely used against various tumors. However, its clinical use is limited by the onset of severe side effects, including ototoxicity and nephrotoxicity. For ototoxicity, a number of evidences in cytotoxic mechanism of cisplatin, including perturbation of redox status, increase in lipid peroxydation, and formation of DNA adduct, have been suggested. Therefore, in this study, the author investigated the relationship between the potassium ions on cisplatin-induced cytotoxicity in HEI-OC1 cells associated with reactive oxygen species (ROS). KCNE1 gene expression by the concentration of intracellular potassium appeared in the plasma membrane and increased the concentration of intracellular potassium. Cisplatin decreased the viability of HEI-OC1 cells, but the KCNE1 gene increased. Also, the KCNE1 gene significantly suppressed generation of intracellular ROS by cisplatin. Western blot analysis showed that the KCNE1 gene increased phase II detoxification enzymes markers such as superoxide dismutase 1 (SOD1), superoxide dismutase (SOD2), NAD(P)H:quinine oxidoreductases (NQO1), which were associated with the scavenger of ROS. These results suggest that the KCNE1 gene for intracellular potassium concentration ultimately prevents ROS generation from cisplatin and further contributes to protect auditory sensory hair cells from ROS produced by cisplatin.

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Prediction of Chemotherapeutic Response in Unresectable Non-small-cell Lung Cancer (NSCLC) Patients by 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) Assay

  • Chen, Juan;Cheng, Guo-Hua;Chen, Li-Pai;Pang, Ting-Yuan;Wang, Xiao-Le
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3057-3062
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    • 2013
  • Background: Selecting chemotherapy regimens guided by chemosensitivity tests can provide individualized therapies for cancer patients. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt (MTS) assay is one in vitro assay which has become widely used to evaluate the sensitivity to anticancer agents. The aim of this study was to evaluate the clinical applicability and accuracy of MTS assay for predicting chemotherapeutic response in unresectable NSCLC patients. Methods: Cancer cells were isolated from malignant pleural effusions of patients by density gradient centrifugation, and their sensitivity to eight chemotherapeutic agents was examined by MTS assay and compared with clinical response. Results: A total of 37 patients participated in this study, and MTS assay produced results successfully in 34 patients (91.9%). The sensitivity rates ranged from 8.8% to 88.2%. Twenty-four of 34 patients who received chemotherapy were evaluated for in vitro-in vivo response analysis. The correlation between in vitro chemosensitivity result and in vivo response was highly significant (P=0.003), and the total predictive accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for MTS assay were 87.5%, 94.1%, 71.4%, 88.9%, and 83.3%, respectively. The in vitro sensitivity for CDDP also showed a significant correlation with in vivo response (P=0.018, r=0.522). Conclusion: MTS assay is a preferable in vitro chemosensitivity assay that could be use to predict the response to chemotherapy and select the appropriate chemotherapy regimens for unresectable NSCLC patients, which could greatly improve therapeutic efficacy and reduce unnecessary adverse effects.

Selective Cytotoxicity of a Novel Platinum (II) Coordination Complex on Human Gastric Cancer Cell Lines and Normal Kidney Cells

  • Jung, Jee-Chang;Kim, Young-Kyu;Yim, Sung-Vin;Park, Seung-Joon;Chung, Joo-Ho;Chang, Sung-Goo;Lee, Kyung-Tae;Rho, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.3
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    • pp.283-291
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    • 1999
  • We have synthesized novel platinum (II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis(diphenylphosphino)ethane (DPPE) as leaving group. Furthermore, nitrate was added to improve the water-solubility. A new series of [Pt(cis-DACH)(DPPE)] $2NO_3(PC)$ was evaluated its antitumor activity on various MKN-45 human gastric adenocarcinoma cell-lines and normal primary cultured kidney cells. The new platinum complex demonstrated high efficacy in the cytotoxicity on MKN-45 cell-lines as well as adriamycin-resistant (MKN-45/ADR) and cisplatin-resistant (MKN-45/CDDP) cells. The cytotoxicities of PC were found quite less than those of cisplatin in rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues using MTT assay, $[^3H]-thymidine$ uptake and glucose consumption tests. Based on these results, this novel platinum (II) coordination complex, was considered as better a valuable lead for improving antitumor activities with low nephrotoxicities in the development of a new clinically available anticancer chemotherapeutic agents.

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Radiation Therapy of Nasopharyngeal Carcinoma (비인두강 종양의 방사선치료성적)

  • Nho Young Ju;Cho Jeong Gill;Ahn Seung Do;Choi Eun Kyung;Kim Jong Hoon;Kang One Chul;Chang Hyesook
    • Radiation Oncology Journal
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    • v.15 no.4
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    • pp.305-313
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    • 1997
  • Purpose : This is a retrospective study to evaluate the results of radiation therapy and prognostic factors influencing the results in nasopharyngeal carcinoma. Materials and Methods: From October 1989 to May 1996. 56 Patients were treated for nasopharyngeal carcinoma at Department of Radiation On-cology. According to stage, patients were distributed as follows : stage I (2), II (13). II (11), IV (30). Twenty-eight patients were treated with radiation therapy only, 7 patients were treated with neoadiuvant chemotherapy followed by radiation therapy. Twenty-one Patients were treated with radiation therapy and weekly CDDP. After external beam radiotherapy of 60Gy, 46Patients received boost dose with intracavitary radiation and 9 Patients with 3D conformal therapy. One patient received boost dose with 2 dimensional Photon beam therapy. The tumor dose ranged from 69.4Gy to 86.2Gy with median dose of 74.4Gy. The follow-up Period ranged from 5 months to 92 months with a median of 34 months. Results : Forty-seven patients achieved complete response and 8 Patients showed partial response. One Patient showed minimal response. Patterns of failure were as follows : locoregional recurrence (8) and distant metastasis (18). Among these patients, 2 patients failed locoregionally and distantly. The sites of distant metastasis were bone (8), lung (8) and liver (4). Five years survival rate was $67.2\%$ and 5 years disease-free survival rate was $53.6\%$. KPS (P=0.005) and response ol radiation therapy (P=0.0001) were significant prognostic factors for overall survival. KPS (P= 0.02) and response of radiation therapy (P=0.005) were significant Prognostic factors for disease-free survival. Conclusion : This retrospective study showed that distant metastasis was the Predominant pattern of relapse in nasopharyngeal cancer Neoadiuvant chemotherapy or weekly CDOP did not influence the distant metastasis-free survival. For advanced T stage, 3D conformal therapy Provided an improved dose coverage compared to ICR But further follow-up was needed in Patients with 3D conformal therapy to assess the efficacy of this therapy. Development of techniques of radiation therapy to improve locoregional control and of more effective systemic chemotherapy regimen are needed.

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