• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2485-2489
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• 2012

Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.

• Tuberculosis and Respiratory Diseases
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• 제57권3호
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• pp.257-264
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• 2004

배 경 : 생존율이 아주 낮은 국소 진행성의 비소세포 폐암에서 생존율 증가 시키기 위한 여러가지 방법이 시도되고 있다. 그 중에서 화학-방사선 동시요법은 치료 반응율은 높아지지만 치료에 따른 부작용 또한 적지 않다. 화학-방사선치료를 병용할 경우에 있어서 항암제의 종류, 용량 및 투여방법과 방사선 조사의 적절한 시기에 관해서 아직 논란이 많은 상태이다. 본 연구는 docetaxel/cisplatin 병용화학요법의 초기에 방사선 치료를 동시에 실시한 환자들의 치료성적과 부작용 및 생존 기간을 알아보았다. 방 법 : 2000년 5월부터 2001년 9월까지 고신대학교 복음병원에 내원하여 비소세포 폐암으로 진단받은 병기 IIIA, IIIB의 환자들 중, 과거 항암치료력이 없고 수술이 불가능한 16명 환자를 분석하였다. 환자는 평균 연령은 58세이고 모두 남자이었다. ECOG 0-1이 14명, 2가 2명이었다. 병리조직학적으로 편평 상피세포암 10명(62.5%), 선암 6명(37.5%)이었다. 병기는 IIIA 2예, IIIB 14 예이었다. 방사선치료는 첫 번째 화학요법을 마친 다음날 1.15 Gy 씩 1일 2회 과분할조사를 시행하여 총 69 Gy를 6주간 조사하였고, 화학치료는 매 3주 주기로 6회 치료를 원칙으로 하였다. 화학요법 제1일에 docetaxel 75 $mg/m^2$를 주입한 후 이어서 cisplatin 60 $mg/m^2$를 정주하였다. 총 6차례 항암 화학 요법을 마친 후 치료반응 및 치료 동안의 부작용 및 생존기간을 조사하였다. 결 과 : 완전 관해는 4명(25.0%), 부분 관해는 12명(75%)으로 모든 환자에서 반응이 있었다. 치료 도중 독성의 빈도는 3도 이상의 백혈구 감소증이 87.5%, 3도 식도염이 68.8%이 발생하였다. 항암 화학 요법은 평균 5.6회(4-6회)실시하였고 백혈구의 감소로 인하여 16명 모두에서 약제 감량을 실시하였고 평균 2.9회에서 이루어졌다. 16명 중 13명이 사망하였고 중앙 생존 기간은 19.9개월(4.3-39.7개월)이고 1년 생존율은 68.7%, 2년 생존율은 43.7%, 3년 생존율은 29.1%이고 무질병 진행 기간은 중앙값이 9.3개월이었다. 추적 조사 중 국소재발은 11예 66.8%이었고, 원격 전이는 3예(18.8%)에서 관찰이 되었다. 원격 전이의 경우 골전이가 2예, 뇌전이가 1예에서 일어났다. 결 론 : 국소 진행성 폐암의 치료로 docetaxel/cisplatin을 3주마다 주사하면서 초기에 화학-방사선 요법을 동시에 실시할 경우에 반응율과 생존율은 우수하였으나 치료에 따른 부작용은 많이 발생하였다. 따라서 향후 부작용을 최소화시키고 치료효과를 최대화시키기 위해서는 약제의 용량, 투여방법 및 방사선치료 시기에 대한 연구가 더 필요할 것으로 생각된다.

• BMB Reports
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• 제50권9호
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• pp.466-471
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• 2017

The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.550-555
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• 2002

The discovery and development of the taxane class of antitumor compounds represent significant advances in the treatment of patients with a variety of malignancies. These drugs are effectively used in the treatment of breast cancer. In this study we evaluated the efficacy of fractionated usage of both paclitaxel and docetaxel as a single agent in the breast cancer cell line MCF-7. It has been shown that the cytotoxic effect of paclitaxel was increased when the divided $IC_{50}$ concentrations were used sequentially and in contrast to paclitaxel, cytotoxic effect of docetaxel was decreased with the same schema and the single dose of $IC_{50}$ concentration was optimal. The cause of the difference between the cytotoxic effects of two agents with this schedule is obscure. Demonstrating mechanisms, which are responsible for these differences, will be important for more rational use of taxoids and to provide basis for the following clinical trials.

• Nutrition Research and Practice
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• 제15권1호
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• pp.12-25
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• 2021

BACKGROUND/OBJECTIVES: The study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms. MATERIALS/METHODS: Using 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting. RESULTS: At concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G0/G1 peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine. CONCLUSIONS: We report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8661-8666
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• 2014

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel $60mg/m^2$ plus cisplatin $60mg/m^2$ (day 1) combined with capecitabine $1650mg/m^2$ (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective first-line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

• Bulletin of the Korean Chemical Society
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• 제30권1호
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• pp.25-26
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• 2009

• 한국임상약학회지
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• 제20권1호
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• pp.30-38
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• 2010

This study was conducted to analyze cost-effectiveness of neoadjuvant chemotherapy for locally advanced head and neck cancer in Korean healthcare setting. We constructed a decision analytical model to estimate total costs and outcomes of paclitaxel+cisplatin (PC) or docetaxel+cisplatin+5-FU (DCF) for 2 years time horizon in 100 patient cohort with locally advanced head and neck cancer. Base analysis showed that cost savings of PC regimen were 379 million Korean Won and 231 million Korean Won in societal and payer's perspectives, respectively, compared to DCF regimen, and life saved was 0.18. PC regimen as a dominant strategy was found to be robust through sensitivity analyses.

• 대한위암학회:학술대회논문집
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• 대한위암학회 2004년도 제17회 춘계학술대회
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• pp.33-33
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• 2004

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.164.1-164.1
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• 2001