• Molecules and Cells
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• 제37권12호
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• pp.857-864
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• 2014

Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the antiapoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADPribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1553-1556
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• 2012

Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7037-7041
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• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• Advances in Traditional Medicine
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• 제1권1호
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• pp.45-54
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• 2000

Cannabidiol derivatives (1, 2 and 3), and 5-fluorouracil (4, 5-FU) were tested for their growth inhibitory effects against human oral epitheloid carcinoma cell lines (KB) using two different 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. These compounds showed a potent inhibitory activity in vitro in the micromolar range against KB cell lines. In general, the antitumor activity of these compounds (1, 2, 3 and 4) was in a dose-dependent over the micromolar concentration ranges from $1\;{\mu}M\;to\;100\;{\mu}M$. The comparison of $IC_{50}$ values of these compounds in tumor cell lines shows that their susceptibility to these compounds decreases in the following order: CBD > 5-FU > CBDME > CBDDE by the MTT assay and SRB assay. Cannabidiol derivatives (1, 2 and 3), and 5-FU were tested for their cytotoxic effects on NIH 3T3 fibroblasts using two different MTT assay and SRB assay. These compounds exhibited potent cytotoxic activities in vitro in the micromolar range against NIH 3T3 fibroblasts. In general, the cytotoxic activities of these compounds (1, 2, 3 and 4) were in a dose-dependent over the micromolar concentration range $1\;{\mu}M\;to\;100\;{\mu}M$. The comparison of $CD_{50}$ values of these compounds on NIH 3T3 fibroblasts shows that their susceptibility to these compounds decreases in the following order; CBD > 5-FU > CBDDE > CBDME by MTT assay, CBD > 5-FU > CBDME > CBDDE by SRB assay. These results suggest that cannabidiol (1, CBD) retains the most growth-inhibitory activity against KB cell lines.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3511-3514
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• 2016

Purpose: To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMT-RT) without surgery. Materials and Methods: A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January $1^{st}$, 2003 and December $31^{st}$, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMT-RT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5-fluorouracil short infusion plus leucovorin and/or capecitabine or 5-fluorouracil infusion alone. All patients received pelvic irradiation. Results: There were 5 patients (10.4%) with a complete pathological response. The 3 year-overall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 year-overall survival rates were 70.3% and 0% (p<0.01). The 5 year-overall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p=0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. Conclusions: The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

• 한국미생물·생명공학회지
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• 제20권2호
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• pp.150-155
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• 1992

토양 분리 균주로부터 얻은 배양액을 20-80 황산암모늄으로 분획한 후 세포의 cytosine deaminase의 성질을 검토하였다. 이 효소는 cytosine과 5-fluorocytosine(5-FC)에 기질 특이성을 가짐으로서 각각 uracil과 5-fluorouracil(5-FU)로 전환을 촉매하였다. 효소안정성에 대한 온도와 보존기간은 tris-HC1 완충용액에서 검토한 결과 최적온도는 $50^{\circ}C$ 부근이하에서 90 이상의 잔존활성을, 보존시간은 4일정도에서 80 이상의 잔존활성을 유지하였다. 최대 pH 8.0과 $37^{\circ}C$의 온도에서 나타났다. 활성에 적당한 pH는 8.0~8.5였고, 온도는 37~$45^{\circ}C$의 범위였다.

• 대한한방내과학회지
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• 제27권2호
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• pp.327-335
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• 2006

Aim: To examine the efficacy of Hominis Placenta Hydrate (HPH) on the hemopoiesis in a myelosuppression model system. Methods: Mice were injected with 5-Fluorouracil (5-FU) intraperitoneally and were administered with 200 mg/kg and 1000 mg/kg of HPH. Peripheral blood was analyzed at 5, 9, and 13 days. Histopathologic examination of bone marrow was performed at 5 days after 5-FU injection. The expression of cytokine involved in hemopoiesis was examined by using ELISA kit. Results: The hematology data demonstrated that the treatment of all the agents augmented monocytes and leucocytes counts in the peripheral blood WBC and platelet in HPH treated group were significant increased compared with control group. Also, cell numbers of RBC and Hb were restored. In HPH treated group, expression of IL-3, GM-CSF was significant increased But not TPO. Conclusions: Based on the above results, it is suggested that Hominis Placenta Hydrate is an effective remedy for the bone marrow failure and myelosuppression occurring during chemotherapy.

• 대한방사선기술학회지:방사선기술과학
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• 제38권4호
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• pp.463-475
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• 2015

본 논문은 상당히 진행된 중위 식도암의 동시항암화학 방사선치료에 대한 분석의 것이다. 사용한 항암제는 전통적으로 사용되어온 시스플라틴, 5-플루오로우라실에, 도쎄탁실을 추가 시행하였다. 과거 식도암의 방사선치료에서는 총 선량 50.4 Gy/28회를 처방하였다. 하지만 현대의 방사선치료기술의 비약적인 발전으로, 호흡동조치료와 세기변조방사선치료를 적용하여, 정상조직의 손상을 최대한 감소시키면서 총 선량을 50.4 Gy이상으로 증가시키는 것이 가능하다. 이에 우리는, 도쎄탁실, 시스플라틴, 5-플루오로우라실 이라는 새로운 3제 병합요법(DCF-R)에 추가하여, 4DCT 모의시뮬레이션을 기반으로 한 호흡동조 세기변조방사선치료(gated-IGRT) 총 선량 70.2 Gy/39회를 동시에 시도하였으며, 치료기간 동안, 그리고 치료 종료 후 임상적으로 환자에게 위중한 합병증 및 부작용 발생은 관찰되지 않았다. 또한 생존율 향상을 이루어 냈다. 이를 바탕으로, 식도암의 새로운 치료방법을 제안한다.

• Radiation Oncology Journal
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• 제11권2호
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• pp.331-335
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• 1993

1981년 1월부터 1991년 12월까지 서울대학교병원 치료방사선과에서 방사선치료를 받은 40명의 국소적으로 절제불가능한 췌장암 환자를 대상으로 후향적 분석을 실시하였다. 방사선치료를 2주의 간격을 두고 2000 cGy씩 총 4000 cGy를 조사하고 5-FU (5-fluorouracil)를 방사선조사의 각 course의 첫 3일에 걸쳐 투여한 40명의 모든 환자에 대해 분석을 하였으며 그중 23명의 환자는 방사선치료 4주 후부터 5-FU 단독 혹은 FAN (5-FU, Adriamycin, Mitomycin)을 유지요법으로 시행하였다. 생존의 중앙치는 9개월이며, 2년 생존율은 $10.0\%$이었다. 통증완화는 $70.0\%$에서 완전 혹은 부분관해를 보였다. 치료전 performance status가 중요한 예후 인자였으며 치료전 고식적 수술을 시행한 군 및 종양이 두부에 위치한 군이 의미 있게 생존율이 높았다.

• Toxicological Research
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• 제31권2호
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• pp.151-156
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• 2015

5-Fluorouracil (5-FU) is commonly used for the therapy of colon cancer; however, acquired resistance to 5-FU is a critical barrier to successful treatment and the primary cause of chemotherapy failure. Epithelial-mesenchymal transition (EMT) is a process whereby cells undergo alterations in morphology and molecular characteristics promoting tumor progression and metastasis. Accumulating evidence shows that transition from epithelial to mesenchymal phenotype in cancer cells is associated with their resistance to chemotherapy. However, it is still poorly understood whether EMT is involved in acquired resistance to 5-FU. In this study, we developed an in vitro cell model, 5-FU-resistant HT-29 colon cancer cells, and characterized the differences in cellular morphology and molecular alterations between parental and resistant cells. In accord with mesenchymal-like morphology of 5-FU-resistant HT-29 cells, the expression of the mesenchymal marker fibronectin was significantly increased in these cells in comparision with that in the parental cells. Of interest, we also found a marked increase in the expression of EMT-inducing transcription factors Twist, Zeb1, and Zeb2. Finally, 5-FU-resistant cells showed enhanced migration in comparison with parental HT-29. Taken together, these results indicate that EMT could be associated with 5-FU resistance acquired by HT-29 cells. A specific role of each transcription factor found in this study will require further investigation.