• Biomolecules & Therapeutics
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• 제30권2호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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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.

• Journal of Chest Surgery
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• 제26권3호
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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.

• Biomolecules & Therapeutics
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• 제8권3호
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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.

• 한국항행학회논문지
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• 제17권3호
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• pp.346-353
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• 2013

소프트웨어 개발의 주요 동향 중 하나는 소프트웨어 산업의 세계화에 있다. 글로벌 소프트웨어 개발은 여러 가지 문제에 직면해 있다. 이러한 문제를 해결하기 위해 새로운 소프트웨어 개발 방법론과 프로세스가 필요하다. 최근 XP 동향에서의 개발 단계로 본다면 기존의 개발자와 개발자간의 협업을 위한 도구에서 벗어나 조직 구성원 전체가 협업할 수 있는 시스템이 필요하다. 텍스트 기반의 IDE 플러그인 형태나 단순한 화면공유, 채팅 기능을 제공하는 것이 아닌 구성원 전체가 협업할 수 있는 분산 페어 개발을 지원하는 시스템의 설계하고 개발하였다.

• 약학회지
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• 제44권5호
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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.

• 대한임상검사과학회지
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• 제45권3호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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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.

• Radiation Oncology Journal
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• 제15권4호
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• pp.305-313
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• 1997

목적 : 비인두강종양의 방사선치료의 결과를 후향적으로 분석하여 방사선치료의 효과와 예후인자를 분석하고자 하였다. 대상 및 방법 : 1989년부터 1996년까지 서울중앙병원에서 비인두강종양으로 진단받고 근치적 방사선치료를 시행한 56명을 대상으로 하였다 병기별로 보면 T1, T2, T3, T4가 각각 17, 10, 11,18명이었고 NO, Nl, N2, N3가 각각 11명, 27명, 4명, 14명이었다. 근치적 방사선치료만 시행한 환자는 28명, 유로항암요법을 병용한 환자는 7명, 매주 CDDP 항암요법을 병용한 환자는 21명이었다. 조사량은 6940-8620cGy였고 중앙값은 7440cGy였다. 외부방사선조사 60Gy이후 원발병소에 대한 부가적치료는 1명은 외부방사선조사, 46명은 강내조사, 9명은 삼차원 입체조형치료를 받았다. 추적관찰기간은 5-92개월이었고 중앙값은 34개월이었다. 결과 : 전치료후 47명은 완전관해, 8명은 부분관해, 1명은 무반응을 보여줬다. 5년 생존율은 $67.2\%$, 5년 무병생존율은 $53.6\%$이였다. 국소재발이 생긴 시기는 6-45개월(중앙값: 14개월)이었으며 전신적 전이가 생긴 시기는 3-49개월(중앙값: 16개월)이었다. 8명의 환자$(14.3\%)$에서 국소재발이 발생하였고 18명의 환자$(32.1\%)$에서 전신적 전이가 발생하였다. T3나 T4 환자 중 강내조사를 받은 20명중 4명$(20\%)$예서 원발병소에 재발이 있었고 삼차원 입체조형치료를 받은 9명중 1명$(11\%)$에서 원발병소에 재발이 발생하였다. 전신적 전이는 골전이가 가장 많았다. 생존율에 영향을 주는 예후인자로는 생존율에는 KPS(P=0.005), 방사선치료에 대한 반응(P=0.0001)이 통계학적으로 유의하였고 무병생존율에는 KPS(P=0.02), 방사선치료에 대한 반응(P=0.005)이 통계학적으로 유의하였다. 국소재발과 관련있는 예후인자는 없었으며 원격전이와 관련있는 예후인자는 Nstage(P=0.06), 병기(P=0.06)가 다소 의미있는 경향을 보였고, 방사선치료에 대한 반응(P=0.009)이 통계학적으로 유의하였다. 결론 : 비인두강종양에서 방사선치료로 5년생존율 $67.2\%$이었고 5년 무병생존율은 $53.6\%$이였다. 재발양상을 보면 국소재발보다는 전신적 전이율이 높음을 알 수 있었고 항암치료와의 병용은 관련이 없었다. T3 혹은 T4 병기에서 삼차원 입체조형치료를 받은 환자에 대해서는 앞으로 추적 관찰이 좀 더 필요할 것으로 생각된다. 앞으로 국소관해를 높이기 위한 방사선치료방법과 전신적 전이율의 감소를 위한 항암요법에 관한 연구가 필요할 것으로 생각된다.