• 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.

• Korean Journal of Veterinary Research
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• v.37 no.3
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• pp.509-523
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• 1997

This study was carried out for investigating antitumor effects of 5-fluorouracil(5-FU), methotrexate(MTX) and retinoic acid(RA) on hepatocellular carcinoma induced in Sprague-Dawley rat. Antitumor effects were examined a flow cytometric DNA distributions by flow cytometry and stuied ATP/Pi using nuclear magnetic resorance, and the enzymatic activity of thymidylate synthetase and dihydrofolate reductase as well as contents of total collagen and sialic acid were measured with spectrophotometer. In this study, S phase fraction, contents of sialic acid and total collagen were decreased in the induced hepatocellular carcinoma treated with 5-FU and MTX, and synergistic effects of anticancer drugs were exhibited in the hepatocellular carcinoma treated with 5-FU and MTX simultaneously, and the inhibition of thymidylate synthetic and dihydrofolate reductase activity were shown in the hepatocellular carcinoma treated with 5-FU, MTX, and 5-FU and MTX simultaneously. On the other hand, the ratio of ATP/Pi were increased in all groups except group treated with RA. The experimental results suggest that above method may be valuable for evaluating antitumor effect of anticancer drugs.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.11-16
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• 2012

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; $25{\mu}g/ml$) and methotrexate (MTX; $50{\mu}g/ml$), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptase-polymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.

• Journal of Korean Academy of Fundamentals of Nursing
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• v.4 no.1
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• pp.147-162
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• 1997

This study was attempted to provide the basic data for nursing intervention to improve the psychosociological adaptation of patients receiving chemotherapy for breast cancer by examining relationship between anxiety and hopelessness that they are experiencing and family support, in order to help them successfully cope with various psychological problems. This study was carried out with 93 breast cancer patients who are receiving chemotherapy in the injection treatment room of K University Hospital located in the downtown of Taegu after having underwent mastectomy in the hospital between December 1995 and August 1996. This study used the systematized questionnaires which contain 7 questions about general characteristics, Spielberger's trait anxiety & state anxiety scale, the tool that WON(1987) modified the hopelessness scale which was developed by Beck et al.(1967) and the family support tool made by TAE(1985). By using the SPSS/PC program, this study obtained the real number and percentage for the general characteristics of the subjects, and mean and standard variation for the degrees of trait anxiety, state anxiety, hopelessness and family support. The correlation between each variables was identified on the basis of the Pearson Correlation, and the degrees of trait anxiety, state anxiety, hopelessness and family support in the general characteristics of the subjects were analyzed by using the t-test, ANOVA, and Duncan test. The results of this study were summarized as follows. In the general characteristics of the subjects, most of each group were 51 years old or more and the middle class in income, had educational background under elementary school, no job, Buddhism in religion and spouse, and were receiving chemotherapy using MTX and 5FU. It was shown that the degree of the subjects' trait anxiety is, on an average, 50. 29, state anxiety 49. 68, hopelessness 51. 46 and family support 34. 28. Both trait anxiety and hopelessness showed normal correlation ; the higher the degree of trait anxiety is, the higher the degree of hopelessness is, while trait anxiety and family support showed reverse correlation ; the higher the degree of trait anxiety, the lower the degree of family support that the subjects perceive is. State anxiety and hopelessness also showed normal correlation ; the higher the degree of state anxiety is, the higher the degree of hopelessness is. Family support and hopelessness showed reverse correlation ; the higher the degree of family support is, the lower the degree of hopelessness that the subjects perceive is. And family support and state anxiety showed reverse correlation but there was a statistically significant difference. The degree of trait anxiety in the general characteristics of the subjects showed a significant difference by age, job and religion, the degree of state anxiety a signigicant difference by job and religion, the degree of hopelessness a signigicant difference by age, educational background and existence or not of spouse. In conclusion, the breast cancer patients receiving chemotherapy perceive anxiety and hopelessness due to several causes such as diagnosis itself or side effects of chemotherapy, so that it is required not only to develop specific nursing interventions including family support to alleviate anxiety and hopelessness but also to apply such interventions to clinical practice.