• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.313-321
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• 2018

Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein ($PrP^C$) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, $PrP^C$ expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, $PrP^C$ increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4. In addition, $PrP^C$ inhibited the activation of the stress-associated proteins p38, JNK, and p53. Moreover, after treatment of 5-FU-resistant CRC cells with 5-FU, silencing of $PrP^C$ triggered apoptosis via the activation of caspase-3. These results indicate that $PrP^C$ plays a key role in CRC drug resistance. The novel strategy of combining chemotherapy with $PrP^C$ targeting may yield efficacious treatments of colorectal cancer.

• Journal of the Korean Chemical Society
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• v.56 no.4
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• pp.473-477
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• 2012

The novel chitosan-based thermosensitive hydrogels were prepared as control-releasing drug carriers. N-carboxyethyl chitosan (ACS) was synthesized by microwave heating for 1 h through Michael addition of CS to acrylic acid in a grafting yield of 52.97%, which was proved to be a faster and more efficient way than ordinary methods. 5-Fu was modified with formaldehyde to synthesize N,N'-Bis(hydroxymethyl)-5-fluorouracil (5-Fu-OH). Then an esterification was performed using ACS and 5-Fu-OH to give 5-Fu-ACS. The new thermosensitive hydrogels were prepared by adding sodium glycerophosphate to the solution of compounds under a certain constant temperature. Simultaneously, the hydrogels' swelling rate, in vitro drug release rate and thermosensitive were studied, and found that the 5-Fu-ACS composite hydrogel had more excellent releasing effect, higher drug loading and better thermosensitive.

• 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.

• Journal of Digestive Cancer Research
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• v.5 no.1
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• pp.58-61
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• 2017

5-Fluorouracil (5-FU) has been widely used in the treatment of various solid tumors. However, 5-FU cardiotoxicity is being reported with increasing frequency. The main symptom of cardiotoxicity is chest pain at rest with ischemic electrocardiographic changes. Up until now, the underlying mechanism has been suspected to be coronary artery spasm. However, this chest pain associated with 5-FU has several characteristics that are incompatible with coronary artery spasm; eg, inefficacy of calcium-channel blocker and a slow increase in cardiac enzyme levels. We experienced a case of 5-FU-induced cardiotoxicity which showed clinical findings consistent with acute myocardial infarction. Based on the clinical findings, coronary angiography, and no stenosis was noted. However, we concluded that the cardiotoxicity in this case was due to ischemia caused by coronary artery spasm. Because vasodilatator was effective and secondary attack was followed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3589-3593
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• 2012

Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid ($200mg/m^2$), glucose 5%, 5-FU ($400mg/m^2$) and 22 hr. CIV ($600mg/m^2$) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid ($20mg/m^2$)for five days, 5FU($425mg/m^2$) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ${\geq}2$ events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.

• 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.

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.121-127
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• 2000

Cannabigerol (1, CBG), methyl 4-[(2E)-3,7-dimethyl-2,6-octad ienyl)oxy]-3-methoxybenzoate (2, DTM), 5-fluorouracil (3, FU) as a reference, and cannabidiol (4, CBD) were tested for their growth inhibitory effects against KB(ATCC NO, OCL 17) cell lines using two different assays, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay and the sulforhod-amine B protein (SRB) assay. These compounds showed inhibitory activity in vitro in the micromolar range against KB cell lines. In general, the antitumor activities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentration range of 1 to 100 M. The comparison of $IC_{50}$ values of these compounds in tumor cell lines showed that their susceptibility to these compounds decreases in the following order: DTM > CBD > 5-FU > CBG by MTT assay and DTM = CBD > 5-FU > CBG by SRB assay. CBG 1, DTM 2, 5-FU 3, and CBD 4 were tested for their cytotoxic effects on NIH 3T3 fibroblasts using two different assays, the 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 acivities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentraion range of 1 to 100 M. The comparison of $CD_{50}$ values of these compounds in NIH 3T3 fibroblasts shows that their susceptibility to these compounds in decreases the following order(:) CBD > 5-FU > DTM > CBG by MTT assay, CBD > 5-FU > CBG > DTM by SRB assay. These results suggest that DTM 2 has the most growth-inhibitory activity against KB cell lines.

• Journal of the Korean Society of Safety
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• v.24 no.4
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• pp.47-52
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• 2009

This study has been to examine the occupational exposure levels of Fluorouracil (5-FU) in a hospital and to investigate the most effective cleaning reagent for control. Fluorouracil is one of the cytotoxic drugs which are therapeutic agents used to treat cancer. The health practitioners working in the cytotoxic work room and oncology ward areas are exposed to adverse health risks like cytogenetic and DNA damage from cytotoxic drugs exposure by frequent skin contact from contaminated surfaces. Four kinds of cleaning reagents has been examined to degrade the 5-FU. It was found that 5-FU was only degraded soon after the reaction in 0.5%(w/v) NaClO solution. Therefore, 0.5%(w/v) NaClO solution has been chosen to decompose any residues on the contamination surfaces. A substantial level of contamination was found on the surfaces of cytotoxic work room and oncology ward areas. The contamination ranges of the surfaces in cytotoxic work room and oncology ward areas were from 2.0 to $13.8{\mu}g/m^2$ and 5.39 to $11.53{\mu}g/m^2$ respectively. Consequently, regulation of the occupational exposure limit, procedure of special cleaning, and the use of personal protective equipment are recommended during the manipulation and administration of the drugs to avoid skin contamination from cytotoxic drugs like 5-FU.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5587-5591
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• 2012

Objective: This study was performed to evaluated the efficacy and safety of continuous infusional paclitaxel and 5-Fu as first-line chemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Methods: A total of 22 patients with advanced esophageal squamous cell cancer with no indications for surgery and radiation therapy, or recurrent patients were enrolled from October 2008 to November 2010. All were treated with PTX 20 $mg/m^2$ was administered through a 16 hours continuous intravenous infusion on days 1 to 3, 8 and 9. DDP 3.75 $mg/m^2$ was given on days 1 to 4 and 8 to 11, continuous infusional 5-FU over 24-hours on days 1 to 5 and 8 to 12 at a dose of 375 $mg/m^2$, and folacin 60 mg orally synchronized with 5-Fu. The treatment was repeated every 21 days for at least two cycles. Results: 22 cases of all enrolled patients could be evaluated for the effect of treatment: 2 cases were CR, 9 cases PR, 5 cases SD and 2 cases PD, giving an overall response rate of 68.2%(15/22). The median time to progression was 7.0 months. The adverse reactions related to chemotherapy were tolerable; the most common toxic effects were marrow depression, alopecia, and fatigue. Conclusion: Low-dose continuous infusional PTX over 16-hours and 5-fu over 24-hours is a promising regimen with good tolerability in treating patients with advanced esophageal squamous cell cancer.

• 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.