• Journal of Pharmaceutical Investigation
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• v.26 no.4
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• pp.281-289
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• 1996

In our previous work, we have studied the effect of lactose and sodium alginate (SA) on the rate of release of 5-fluorouracil (5-FU) from ethylene-vinyl acetate (EVA) matrix. These hydrophilic additives promoted the rate of 5-FU release and the increase in rate was larger when SA was used. Both additives showed better ability to increase the rate than 5-FU itself. In this paper, we extended our study to another hydrophilic additive, Carbopol 940 (CP). Compared to SA or lactose, CP increased the rate of 5-FU release markedly. Release rate increased as the loading amount and the pH of the release medium increased. After release experiment, matrix volume increased up to 15 times of that before release experiment, depending on the amount of CP dispersed in the matrix and the pH of the release medium. On the other hand, the volume of the matrix containing lactose or SA decreased. The weight changes of the dry matrix before and after release experiment imply that CP is not released out of the matrix, to the contrary of lactose and SA. Scanning electron microscope study clearly showed that large cavities and pores are generated on the surface and the inside of the matrix. These results indicate that the mechanism by which CP increases the release rate is quite different from that of monomeric additives such as lactose or SA.

• Toxicological Research
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• v.31 no.2
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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.

• Bulletin of the Korean Chemical Society
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• v.31 no.8
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• pp.2235-2241
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• 2010

A reverse-phase HPLC method with detection by mass spectrometry is described for the simultaneous determination of doxifluridine and its two active metabolites, 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUrd), in beagle dog plasma. The optimal chromatographic separation was achieved on a Waters $Xterra^{(R)}$ $C_{18}$ column ($4.6{\times}250\;mm$ i.d., $5\;{\mu}m$ particle size) with a mobile phase of 0.1% formic acid in a mixture of 99% methanol and purified water (99:1, v/v). The developed method was validated in beagle dog plasma with a lowest limit of quantification of $0.05\;{\mu}g/mL$ for both doxifluridine and 5-FU, and $0.2\;{\mu}g/mL$ for 5-FUrd. Doxifluridine and its two metabolites were stable under the analysis conditions, and intra- and inter-day accuracies exceeded 92.87%, with a precision variability ${\leq}11.34%$ for each analyte. Additionally, the method for quantifying doxifluridine and its two metabolites, 5-FU and 5-FUrd, in beagle dog plasma was applied successfully to the analysis of pharmacokinetic samples.

• The Journal of Internal Korean Medicine
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• v.28 no.2
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• pp.304-320
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• 2007

Objective : To evaluate the effect of Astragalus Membranaceus Extrac (AME) on myelosuppression, activity and immune modulation in 5-fluorouracil (5-FU) treated mice. Method : We carried out complete blood count, histological analysis of bone marrow, and cell colony forming assay for hematopoietic progenitor to evaluate the effect of AME on myelosuppression and conducted swimming test, survival rate, nitric oxide (NO) assay, 51Cr release assay in natural killer cell, mRNA expression of $IL-1{\beta}$, IL-2, IL-4, IL-6, IL-10, $TNF-{\alpht}$, $IFN-{\gamma}$, $TGF-{\beta}$ and GM-CSF in spleen cells to evaluate the effect of AME on quality of life (QOL). Results : AME improved 5-FU induced myelosuppression and peripheral blood count was recovered effectively, had significant efficacy to protect against chemotherapy induced marrow-destruction and on hematopoiesis compared with the control group, improved increase survival rate and the swimming time, had a stimulatory effect on macrophage activation and NK cell activity, and up-regulated cytokine gene transcription (IL-2, IL-6, $IFN-{\gamma}$) in murine immunologic system. Conclusion : We can conclude that AM is an effective herbal agent for improvement of myelosuppression and QOL in 5-FU treated mice.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.331-335
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• 1993

From January 1981 to December 1991, forty patients with localized advanced carcinoma of the pancreas were treated at the Department of Therapeutic Radiology, Seoul National University Hospital. The treatment protocol consisted of two split course external radiation therapy with each 2000 cGy over two weeks separated by two week rest period. Intravenous 5-fluorouracil (5-FU) was administered on the first three days of each radiotherapy course. Twenty three of these patients were treated by maintenance 5-FU or FAM (5-FU, adriamycin, mitomycin) chemotherapy. Median survival was 9 months and the 2-year survival rate was $10.0\%.$ Good prognostic indicators were good performance status, palliative bypass surgery and tumor located in the head of pancreas.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.60-64
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• 2002

Background: Chemotherapy with 5-fluorouracil (5-FU) has been one of the mainstay in breast cancer treatment. The effects of high dose 5-FU on cell cycle regulation were studied in breast caner cells. Methods: A breast cancer cell line MCF-7 was used. Protein expressions of G1/S cyclins, $p21^{Waf1/Cip1}$, cdk2, E2F1 and retinoblastoma were tested by western blot analysis. Immunoprecipitation and immune complex kinase assay were done for the assessment of E2F1/RB interacton and the activity of cdk2 respectively. Results: $p21^{Waf1/Cip1}$ expression was barely detectable in control cells. With addition of 5-FU level of $p21^{Waf1/Cip1}$ were induced and cyclin D3 level was decreased as cell growth decreases. In accordance with increased expression of $p21^{Waf1/Cip1}$, cyclin E-associated cdk2 kinase activity was reduced. Retinoblastoma protein (RB) became dephosphorylated and E2F-1 binding activity with RB was increased. Conclusion: In this situation of high concentration of 5-FU breast cancer cells tend to be G1/S cell cycle arrested. Overexpression of $p21^{Waf1/Cip1}$ and dephosphorylation of RB may mediate the effectss of 5-FU by inhibiting E2F-1 activity, which contributes to G1/S cell cycle arrest. These results could be an indicating landmark for further study of high dose chemotherapy with 5-FU.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5529-5533
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• 2014

Background: The aim of this study was to investigate the effect of a c-myc antisense oligodeoxynucleotide and 5-fluorouracil on the expression of c-myc, invasion and proliferation of HEPG-2 liver cancer cells. Materials and Methods: HEPG-2 cells were treated with lipiosome-mediated c-myc ADSON and 5-fluorouracil. The proliferation inhibition rate and invasion were measured by MTT and invasion assay, respectively. Cell apoptosis was detected by flow cytometry and expression of c-myc by RT-PCR and immunohistochemistry. Results: The proliferation inhibition rate was significantly higher in the antisense oligodeoxynucleotide added-5-fluorouracil group than single antisense oligodeoxynucleotide or 5-fluorouracil group (p<0.05). G0/G1 cells in the antisense oligodeoxynucleotide group and S cells in the 5-fluorouracil groups were significantly increased than that in the control group, respectively (P<0.01). The amplification strips of PCR products in 5-FU, ASODN and combination groups were significantly weaker than that in the control group (P<0.01). The percentage of c-myc-protein-positive cells were significantly lower in antisense oligodeoxynucleotide, 5-fluorouracil and combination groups than that in the control group (P<0.01). Conclusions: A liposome-mediated c-myc antisense oligodeoxynucleotide and 5-fluorouracil can inhibit the proliferation and invasion of liver cancer cells by reducing the expression of c-myc. A c-myc antisense oligodeoxynucleotide can increase the sensitivity of liver cancer cells to 5-fluorouracil and decrease the dosage of the agent necessary for efficacy, providing an experimental basis for the clinical therapy of liver cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.387-390
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• 2012

A combination of 5-fluorouracil plus actinomycin D (5FU plus Act D) is the regimen that has been commonly administered to Chinese and Japanese gestational trophoblastic neoplasia patients as the first or second line of treatment with an excellent outcome. However, the efficacy of this regimen in a salvage setting was unclear. To evaluate the efficacy and safety of the 5 FU plus Act D regimen utilized in this condition, all GTN patients resistant to at least three previous chemotherapy regimens who received the 5 FU plus Act D regimen between August 2009 and January 2011 at Chiang Mai University Hospital were reviewed. There were five cases who met the criteria. Four of those patients were in FIGO stage III to IV with a WHO scoring of more than 12. The median number of cycles for each patient was two and only one case achieved remission while four of the cases were unresponsive. The toxicity was evaluated in 12 cycles. Common complications were uncomplicated myelosuppression and mucositis. In conclusion, this regimen revealed modest efficacy in a salvage setting with manageable toxicity.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.431.1-431.1
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• 2002

Gemcitabine demonstrated modest activity in locally advanced and metastatic pancreatic cancer with difficulty early diagnosis and poor prognisis. The purpose of this study was to evaluate the efficacy and toxicity of gemcitabine and 5-fluorouracil(GF) combination theraphy and epirubiciil, cisplatin. and 5-fluorouracil(ECF) combination theraphy for the patients with locally advanced or metaststic pancreatic cancer. Between January 1996 and December 2001, Patients with locally advanced or metastatic pancreatic cancer were selected and reviewed retrospectively at Kangnam St. Mary's Hospital. (omitted)

• Advances in Traditional Medicine
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• v.1 no.1
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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.