• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.146-149
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• 2002

To evaluate the protective effect of Ziziphi Jujubae Semen(ZJS) on 5-Fluorouracil(5-Fu) in cultured vestibular neurons(VN), neurotoxicity was assessed by XTT assay after VN was exposed to 3-24ug/ml 5-Fu for 48 hours. and also, the neuroprotective effect of ZJS was measured by XTT assay in these cultrures. Cell viability was remarkably decreased dose-dependently, after the treatment with 12ug/ml 5-Fu to cultured VN for 48 hours. In the neuroprotective effect of ZJS on the toxicity induced by 5-Fu, ZJS prevented the neurotoxicity induced by 5-Fu in these cultures. From above the results, it suggests that 5-Fu is toxic in cultured VN and herb extract, ZJS has protective effect over the neurotoxicity induced by 5-Fu.

• Journal of Life Science
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• v.26 no.9
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• pp.1015-1021
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• 2016

5-fluorouracil (5-FU), a pyrimidine analog, is a widely used anticancer drug, which works through irreversible inhibition of thymidylate synthase. In the present study, it was investigated the anti-proliferative effects and molecular mechanisms of 5-FU using Ewing's Sarcoma CHP-100 Cells. The present data indicated that treatment of 5-FU to CHP-100 cells induced a G1 phase arrest of the cell cycle in a time-dependent manner. 5-FU-induced G1 arrest was correlated with the accumulation of the hypophosphorylated form of the retinoblastoma protein (pRB) and association of pRB with the transcription factors E2F-1 and E2F-4. Although 5-FU treatment did affect the levels of cyclin-dependent kinases, the levels of cyclin A and B were markedly down-regulated as compared with the untreated control group. In addition, 5-FU-induced G1 arrest of CHP-100 cells was also associated with the induction of apoptosis, as determined by apoptotic cell morphologies, degradation of poly(ADP-ribose) polymerase and Annexin V staining. Furthermore, 5-FU induced the loss of mitochondrial membrane potential with up-regulated pro-apoptotic Bax expression, down-regulated anti-apoptotic Bcl-2 expression and cytochrome c release from mitochondria to cytosol. Collectively, the data suggest that 5-FU is effective in inducing cell growth reduction and apoptosis, in part, by reducing phosphorylation of pRB and activating mitochondrial dysfunction in CHP-100 cells.

• Applied Microscopy
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• v.27 no.2
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• pp.165-175
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• 1997

This paper aims to prove the effects of Squalene (SQ) on the cellular toxicity of 5-FU to the mouse which pretreated with SQ and then treated with 5-FU. The results of the group A (treated with only 5-FU) are as follows. The nucleus was destroyed at 24 hours and 48 hours group, however, somewhat repaired at 72 hours group. The dilated inner cavity and the irregular lamellae of the rough surfaced endoplasmic reticulum (RER) were observed continually until 72 hours group. The inner cavity of the smooth surfaced endoplasmic reticulum (SER) were dilated in all groups. However, the destroyed and the normal membrane were observed simultaneously at 72 hours group. The inner membrane of the mitochondria were almost repaired at 96 hours group. The results of the group B (treated with 5-FU and squalene) are as follows. The nucleus was a little influenced by the toxicity of 5-FU at 24 hours and 48 hours, RER were observed to keep the typical lamella structure of cisternae from 24 to 72 hours group, but inner cavity kept on dilating. In SER, inner cavity were also observed to flatten from 24 to 72 hours group. Mitochnodria were always shown normal. All cell organelles were simillar to those of normal groups at 96 hours. Accordingly, it can be said that the treatment of 50 prevents the cytotoxicity of 5-FU on cell organelles of liver cell and that is concerned with the formation of membrane system of cell organelles.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.604-609
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• 2016

5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that ${\alpha}$-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of ${\alpha}$-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that ${\alpha}$-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated ${\alpha}$-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that ${\alpha}$-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.250.2-251
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• 2003

There are contradicting reports on the nephrotoxicity of heptaplatin, a new platinum derivative. A retrospective study was performed to compare the toxicities of heptaplatin-containing regimens with the ones not. Seventy-seven patients with advanced gastric cancer who did not receive any chemotherapy within the last 3 months before the treatment were evaluated. Among them 38 patients received heptaplatin-containing regimens (heptaplatin/epirubicin/5-FU: 26, heptaplatin/5-FU: 12) and 39 patients received other regimens (cisplatin/epirubicin/5-FU:11, epirubicin/leucovorin/5-FU: 28). (omitted)

• Molecules and Cells
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• v.28 no.2
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• pp.119-124
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• 2009

Anti cancer agent 5-FU (Fluoro Uracil) is a prodrug that can be metabolized and then activated to interfere with RNA and DNA homeostasis. However, the majority of administered 5-FU is known to be catabolized in vivo in the liver where Dihydropyrimidine dehydrogenase (DPD) is abundantly expressed to degrade 5-FU. The biological factors that correlate with the response to 5-FU-based chemotherapy have been proposed to include uridine phosphorylase (UPP), thymidine phosphorylase (TPP), p53 and microsatellite instability. Among these, the expression of UPP is known to be controlled by cytokines such as $TNF-{\alpha}$, IL1 and $IFN-{\gamma}$. Our preliminary study using a DNA microarray technique showed that basic fibroblast growth factor (bFGF) markedly induced the expression of UPP1 at the transcription level. In the present study, we investigated whether bFGF could modulate the expression of UPP1 in osteo-lineage cells and examined the sensitivity of these cells to 5-FU mediated apoptosis.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.545-550
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• 2021

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

• Polymer(Korea)
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• v.31 no.5
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• pp.447-453
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• 2007

In this study, we fabricated recrystallized PLGA (rPLGA) particles using the vacuum drying method. In order to investigate an applicability of the rPLGA particles for controlled release system of 5-fluorouracil (5-FU) loaded PLGA wafer, we prepared three different wafers using; 1) untreated PLGA (uPLGA), 2) rPLGA, and 3) uPLGA and rPLGA (4 : 1, 1 : 1 or 1 : 4). The rPLGA particles were characterized using NMR, IR and GPC to compare with uPLGA particles. The surface and cross section morphology of the prepared wafers were observed by the scanning electron microscope. The release profile of the 5-FU loaded wafer was measured by HPLC. The 5-FU/rPLGA wafer released the incorporated 5-FU in a sustained manner with low initial burst compared to 5-FU/uPLGA. These results showed that the ratio of pure PLGA/recrystallized PLGA can affect the release behaviors.

• The Journal of Korean Medicine
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• v.33 no.2
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• pp.47-55
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• 2012

Objectives: This study aimed to investigate the preventive effect of red ginseng (RG) on 5-fluorouracil (5-FU)-induced side effects focusing on myelosuppression. Methods: Rats (n = 50) were divided into five groups, nave, control (ip, 5-FU injection of 150 mg/kg), and RG pre-treatment (po, 25, 50 and 100 mg/kg for 5 days before 5-FU injection). On the $7^{th}$ day after 5-FU injection, we evaluated the effects using peripheral hematological parameters, colony-forming assay, cytokine levels and histopathological finding. Results: The peripheral white blood cell and the differential count were dramatically suppressed by 5-FU, while RG (50 and 100 mg/kg) treatment significantly improved total white blood cell, neutrophil, lymphocyte and platelet counts. Also, RG (100 mg/kg) pre-treatment significantly increased the number of CFU-GM colony compared with the control group. RG pre-treatment also ameliorated the histopathological damage in bone marrow, spleen, stomach and small intestine tissue. Conclusions: These results demonstrate that Korean RG has preventive effects against 5-FU-induced myelotoxicity and gastrointestinal damage.

• International Journal of Oral Biology
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• v.41 no.1
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• pp.25-32
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• 2016

The tongue has 4 kinds of papillae, which are filiform, fungiform (FU), foliate (FO) and circumvallate papilla (CV). Tongue papillae except filiform papilla include taste buds. The papillae differ in taste sensitivities, likely due to differential expression of taste receptors. In this study, we evaluated differences in the expression levels of taste receptors in FU, FO and CV. Male DBA2 mice, 42-60 days old, were used in the study. Messenger RNAs were extracted from the murine epithelial tissues including FU, FO and CV. Cloned DNAs were synthesized by reverse transcription. Quantitative PCRs (qPCRs) were performed to determine mRNA expression levels of taste receptors. Results of qPCR revealed that the relative expression levels and patterns were different among FU, FO and CV. All three type 1 taste receptors were expressed FU, FO and CV at varying relative expression levels. All 35 kinds of type 2 taste receptors showed higher expression in FO and CV than in FU. Tas2r108 and Tas2r137 showed the two highest expression levels in all tested papillae. The differential expression levels and patterns of taste receptors among the three papillae could contribute to the different physiological sensitivities by tongue areas. Additional studies such as in situ hybridization or taste receptor cell activity recording is necessary to elucidate the functional relationship between expression levels of taste receptors and taste sensitivity.