• Journal of Gastric Cancer
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• v.16 no.3
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• pp.177-181
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• 2016

Purpose: The International Organization for Standardization-5fluorouracil (FU) 10 trial found that bolus 5-FU and l-leucovorin was not inferior to S-1 in the treatment of gastric cancer (GC). Continuous 5-FU and the rapid injection of 5-FU have different anti-cancer effects. Thus, bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. Materials and Methods: We retrospectively analyzed the medical records of all patients with S-1 or capecitabine-resistant, unresectable, or recurrent GC treated with bolus 5-FU and l-leucovorin between January 2010 and December 2015 at Hokkaido University Hospital. The bolus 5-FU and l-leucovorin regimen consisted of intravenous l-leucovorin ($250mg/m^2/2h$) and bolus 5-FU ($600mg/m^2$) administered once weekly followed by a 2-week rest period; each cycle was repeated every 8 weeks. Results: A total of 14 patients were identified. The disease control rate was 35.7%. The median progression-free survival was 1.6 months (95% confidence interval [CI], 1.3~2.0 months), and the median overall survival was 6.3 months (95% CI, 4.7~7.9 months). No patient died from treatment-related causes. The most common severe adverse event associated with bolus 5-FU and l-leucovorin was neutropenia, which occurred in 21.4% of patients. Conclusions: Bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. We are planning a multi-center prospective phase II trial to evaluate the efficacy and safety of bolus 5-FU and l-leucovorin treatment for pre-treated unresectable or recurrent GC to confirm the results of this limited, retrospective study.

• The Journal of Korean Medical History
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• v.29 no.2
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• pp.17-33
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• 2016

Objectives : The goal of this paper is to verify the hypothesis that the diagrams of liver from MingTangZangFuTu (明堂臟腑圖) were derived from ZangFu diagrams (臟腑圖) before northern Song Ages. Methods : The difference of form of liver was analyzed by means of 4 factors, e.g. shape, number, veins and a petiole of leafs, in diagrams from YanLuoZiNeiJingTu [煙蘿子內境圖], OuXiFanWuZangTu [歐希範五臟圖], CunZhenTu [存眞圖], MingTangZangFuTu and ones of liver from Taoism and MingTangZangFuTu. Results : Diagrams of whole body and liver from MingTangZangFuTu were first found in ZhenJiuJuYing (鍼灸聚英). Among them, lobed shape was first found in YanLuoZiNeiJingTu (in Wudai [五代]), a petiole in OuXiFanWuZangTu (northern Song Ages) and 7 leafs in WuZangLiuFuTu (五臟六腑圖. from Tang (唐) Ages to early northern Song Ages. unknown author.), one of references of UiBangNyuChwi (醫方類聚) (1455). However, veins of leafs were drawn in no diagrams. Conclusions : In diagrams of liver from MingTangZangFuTu, shape and a petiole of leafs were based on diagrams of ZangFu before northern Song Ages, but 7 leafs came from WuZangLiuFuTu. However, veins of leafs were not derived from any diagrams in same period.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5127-5131
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• 2013

Background: 5-fluoro-uracil (FU) is a common agent in postoperative chemoradiation in gastric adenocarcinoma. However, FU is not well tolerated in a significant proportion of patients. Capecitabine (CA) is an orally administered fluoropyrimidine carbamate which is preferentially converted to active 5-FU and is one of the agents used instead of FU in such cases. We compared the toxicity, local and distant control and survival rates with FU or oral CA during the course of concurrent radiotherapy to assess the role of CA used instead of FU. Materials and Methods: We conducted an analysis of survival, disease control and toxicity data in 46 patients treated with postoperative chemoradiation following total or subtotal gastrectomy for gastric adenocarcinoma with either FU or CA between January 2008 and December 2012. Results: Median follow-up was 19 months (range: 3-59), median survival time was 23 ({\pm}6.08) months and 1-3 years overall survival (OS) rates were 64.9-39% for all patients. Compared with the CA regimen, the incidence of treatment interruption was higher with FU (p=0.023), but no significant differences were seen in local control (p=0.510), distant recurrences (p=0.721) and survival rates (p=0.866) among patients. Conclusions: Concurrent CA with radiotherapy seems to be a more tolerable and an equally effective regimen for the postoperative treatment of gastric adenocarcinoma when compared to FU.

• Korean Journal of Acupuncture
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• v.24 no.2
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• pp.19-43
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• 2007

Objectives : The aim of this study was to analyse the symptoms of a disease and to elucidate the meaning and rationale of point selection in YuLongFu. Methods : We translated YuLongFu into Korean and analyzed symptoms based upon a comparison of YuLongFu with YuLongGe. The meaning and rationale of point selection in YuLongFu was then inferred from the analysis above. Results and Conclusions : Total 84 acupoints were used in YuLongFu. Moxibustion and pricking blood therapy were used twice. Generally, threre are a lot of diseases caused by stagnation of Qi and blood in YuLongFu. Point selection, therefore, was usually aimed at promoting flow of Qi and blood.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.1-15
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• 2006

Objectives : The aim of this study was to analyze the symptoms of a disease and to elucidate the meaning and rationale of point selection in YuLongFu. Methods : We translated YuLongFu into Korean and analyzed symptoms based upon a comparison of YuLongFu with YuLongGe. The meaning and rationale of point selection in YuLongFu was then inferred from the analysis above. Results and Conclusions : Total 46 points (6 points were repeated) were used in YuLongFu. These points included the collateral Meridian, the four seas, five shu points, lower confluent points, yuan points and eight influential points. Moxibustion and pricking blood therapy were used twice. Generally, threre are a lot of diseases caused by stagnation of Qi and blood in YuLongFu. Point selection, therefore, was usually aimed at promoting flow of Qi and blood.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7611-7615
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• 2014

Aims: To prepare 5-fluorouracil (5-Fu) nanoparticles with higher encapsulation efficiency and drug loading, and then investigate interaction with the SGC-7901 gastric cancer cell line. Materials and Methods: Prescription was optimized by orthogonal experiments, the encapsulation efficiency and loading capacity were tested by high-performance liquid chromatography, and inhibition of proliferation by 5-Fu nanoparticles and 5-Fu given to cells for 24, 48 and 72 hours was investigated by methyl thiazolyl tetrazolium assay (MTT). In addition, 5-Fu nanoparticles were labeled by fluorescein isothiocyanate (FITC), and absorption into cells was tested by flow cytometry. Results: The optimal conditions for preparation were concentrations of 5-Fu of 5mg/ml, of $CaCl_2$ of 60 mg/ml and of chitosan of 2 mg/ml. With a stirring speed of 1200rpm, encapsulation efficiency of 5-Fu nanoparticles was $55.4{\pm}1.10%$ and loading capacity was $4.22{\pm}0.14%$; gastric cancer cells were significantly inhibited by 5-Fu nanoparticles in a time and concentration dependent manner, and compared to 5-Fu with slower drug release, in a certain concentration range, inhibition with 5-Fu nanoparticles was stronger. 5-Fu nanoparticles were absorbed by the cells in line with the concentration. Conclusions: 5-Fu nanoparticles can inhibit growth of gastric cancer cells in vitro to a greater extent than with 5-Fu with good adsorption characteristics, supporting feasibility as a carrier.

• Macromolecular Research
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• v.11 no.3
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• pp.183-188
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• 2003

The controlled delivery of anticancer agents using biodegradable polymeric implant has been developed to solve the problem of penetration of blood brain barrier and severe systemic toxicity. This study was performed to prepare 5-FU-loaded poly (L-lactide-co-glycolide) (PLGA) wafer fabricated microparticles prepared by two different method and to evaluate their release profile for the application of the treatment of brain tumor. 5-FU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC). SEM observation of the 5-FU-loaded PLGA microparticles prepared by rotary solvent evaporation method showed that 5-FU was almost surrounded by PLGA and significant reduction of crystallinity of 5-FU was confirmed by XRD. In case of release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by mechanical mixing, the release profile of 5-FU followed near first order release kinetics. In contrast to the above result, release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by rotary solvent evaporation method followed near zero order release kinetics. These results indicate that preparation method of the 5-FU-loaded PLGA microparticles to fabricate into wafers was contributed to drug release profile.

• Archives of Pharmacal Research
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• v.12 no.3
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• pp.186-190
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• 1989

The release rates of methotrexate (MTX) from MTX-human serum albumin (HSA) conjugate, and 5-fluorouracil (5-FU) from 5-FU acetic acid (AA)-HSA conjugate were determined after incubation of the conjugates in various conditions. The concentrations of 5-FU released from the conjugate increased monoexponentially, however those of MTX increased biexponentially in all studies. It indicated that there are two distinct types of MTX-HSA linkage, weakly and tightly bound linkages. The release rates of 5-FU were lower than those of MTX in all studies indicating that the bond of 5-FU-AA-HSA conjugate is very stable, which is supported by the higher value of activation energy (39. 9 vs 10. 7 Kcal/mole) using Arrhenius equation. The release rates of MTX and 5 -FU from the conjugates increased with incubation temperatures. Proteolytic enzyme and liver homogenates accelerated significantly the release rates of MTX and 5-FU. Approximately 1.30 and 22.0% of MTX were released after 12 hours of incubation in the absence and presence of protease, respectively. The corresponding values for 5-FU were released after 12 hours of incubation with rat liver homogenates which were diluted 6 times with phosphate buffer of pH 6.0. The MTX-HSA and 5-FU-AA-HSA conjugates were very stable in rat plasma.

• Radiation Oncology Journal
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• v.7 no.1
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• pp.1-13
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• 1989

Effects of ionizing radiation alone and combined with chemotherapy on tumor growth and it's clonal specificity monitored by changes in distribution of chromosome number were studies in A549 ceil line originated from human adenocarcinoma of the lung. Radiation (300 rad, 600 rad and 900 rad) were delivered with or without 5-FU. Forty eight hours later, 57.5% of growth inhibition of cell w8s seen in cells treated with 5-FU concentration of $0.4{\mu}g/ml$ for 24hr exposure. Cell survival curves after radiation with and without 5-FU were made. Chromosomal analysis of cells in metaphase in control, and in cells treated with 300 rad of radiation, or $0.4{\mu}g/ml$ of 5-FU treatment, and combined treatment of both were done to examine the changes in ploidy and number of chromosome. Radiation combined with S-FU enhanced growth inhibition of A549 cells. However, no evidence of synergegic effects in growth. inhibition was observed in the cells treated with the combination therapy. Pattern of chromosomal distribution of survived cells were shifted from hyperploidy to hypoploidy by single dose of radiation (300 rad). As radiation dose increased a large number of hypoploidy cells were observed. Following treatment of cells with 5-FU, chomosomal distribution of survived cells were also shifted to hypodiploidy which were seen in cells treated with radiation, The ceil treated with 5-FU and fellowed by radiation within 24 hrs had cell with increased number of hypodiploidy cells. Almost same type of chromosomal changes were reproduced in cells treated with combined treatment with radiation and 5-FU. Minor differences were that cells with fewer number of chromosome were more frequent in cells treated with combined therapy. Further increase in cells of hypoploidy (93%) having 1-10 chromosome were induced by additional radiation. Therefore, the enhanced therapeutic effect of 5-FU combined with radiation of A549 cells appeared to be additive rather than synergistic.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.161-168
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• 2004

5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.