• Title/Summary/Keyword: fluorouracil

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1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation

  • Hyoeun Jeon;Jungeun Yu;Jung Me Hwang;Hye-Won Park;Jiyeon Yu;Zee-Won Lee;Taesoo Kim;Jaerang Rho
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.43.1-43.12
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    • 2022
  • Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

Low-Dose Docetaxel/Cisplatin - Leucovorin and 46 Hour Infusional Fluorouracil in Metastatic Gastric Carcinoma

  • Alici, Suleyman;Buyukberber, Suleyman;Alkis, Necati;Benekli, Mustafa;Ozkan, Metin;Bilici, Ahmet;Demirci, Umut;Karaca, Halit;Arpaci, Erkan;Gumus, Mahmut;Altunbas, Mustafa;Dane, Faysal;Turk, H. Mehmet;Anatolian Society of Medical Oncology
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.423-427
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    • 2013
  • Background: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastric cancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen). Patient and methods: Chemotherapy-naïve patients with metastatic gastric cancer (MGC) received D 60 mg/$m^2$ on day 1 and cisplatin 30 mg/$m^2$ on day 1-2 and the De Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/$m^2$/46h continuous infusion) every 3 weeks. The primary endpoint was response rate. Results: One hundred twenty patients with a median age of 52.5 years (range, 32-78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable patients, 4 showed complete remission and 36 achieved a partial response. The overall response rate was 56.6%. Twenty eight patients (23.3%) showed stable disease and 52 (43.3%) progression. The median time to progression was 7 months (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The most frequent hematological toxicity was leucopenia, which occurred at grade 3/4 intensity in 24 patients (20%). Conclusions: Low-dose DC-De Gramont regimen is active in MGC with a tolerable toxicity profile.

Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

  • Liang, Yong;Bu, Jun-Guo;Cheng, Jin-ling;Gao, Wei-Wei;Xu, Yao-Can;Feng, Jian;Chen, Bo-Yu;Liang, Wei-Chao;Chen, Ke-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6011-6017
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    • 2015
  • Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.

Synergistic Effects of 5-Fluorouracil (FU) and Curcumin on Human Cervical Cancer Cells (5-fluorouracil과 curcumin의 복합투여에 의한 자궁암세포의 성장억제와 p53유전자 발현의 상승 효과)

  • Ahn, Seong-Ho;Kim, Dong-Heui;Kang, Jung-Hoon;Lee, Myeong-Seon
    • Applied Microscopy
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    • v.40 no.4
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    • pp.229-235
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    • 2010
  • Cervical cancer is associated with low antioxidant status. It has a high prevalence especially amongst woman in Asia and is a leading cause of cancer death. Cancer chemotherapy in vivo improved in cases with high p53 expression in the tumor tissue. The restoration of p53 levels could be a potential strategy to increase chemoresponsiveness. Under circumstances where damage is extensive, p53 plays a direct role in trigering apoptosis. To investigate the effect of curcumin (CMN) as an antioxidant agent on anticancer agent 5-fluorouracil (5FU) induced apoptosis and p53 expression, HPV-18 positive HeLa cells were treated with noncytotoxic amounts of antioxidant. Curcumin induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. CMN caused upregulation of p53 expression, evident from Western blotting data and also increased the susceptibility/apoptosis induced by 5FU. These results show that increasing drug sensitivity of cervical cancer cells by upregulation of p53 using CMN is novel approach and could have a possible therapeutic potential in cervical cancer.

Cytokine production profiles of a model for fluorouracil and UVB-induced discoid lupus erythematosus in TCR $\alpha$ chain knockout mouse

  • Yoshimasu, Takashi;Hiroi, Akihisa;Ohtani, Toshio;Uede, Koji;Furukawa, Fukumi
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.494-496
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    • 2002
  • Fluorouracil (FU) is well known to induce discoid lupus-like eruption at the sun exposure sites in Japan. It means the associations of UVB with drug induced DLE. It is still obscure which cytokines are involved in the development of DLE. To address the issue, we established a murine model of FU and UVB-induced discoid lupus and could show the Th1 dominant cytokine profiles in DLE model of TCR $\alpha$ chain KO mice treated with FU and UVB.

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Antitumor Evaluation of Cannabidiol and Its Derivatives by Colorimetric Methods

  • Baek, Seung-Hwa;Shin, Ji-Hee;Chung, Woo-Young;Han, Du-Seok
    • Toxicological Research
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    • v.16 no.2
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    • pp.101-107
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    • 2000
  • Cannabidiol derivatives (1, 2 and 3), 5-fluorouracil (4, 5-FU) and adriamycin (5, AM) were tested for their growth inhibitory effects against human tumor cell lines using two different 3-{4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. The light microscopic study showed morphological changes of the treated cells. Disruptions in cell organelles were determined by colorimetric methods; MTT assay and STB assay. These results suggest that cannabidiol (1, CBD) retains the most growth-inhibitory activity against human tumor cell lines.

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Synthesis of Block Copdymers Consistin(3 of Poly($\tau$-benzy1 L-glutamate) and Polyoxpropylene and Their Drug Release Behsviours (Poly($\tau$-benzy1 L-glutamate)와 polyoxpropylene으로 된 블록 공중합체의 합성 및 약물방출특성)

  • 강인규;김우식
    • Journal of Biomedical Engineering Research
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    • v.13 no.1
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    • pp.55-64
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    • 1992
  • AB -type block copolymers of poly($\tau$-benzyl L-glutamate) (PBLG, a segment) and polyoxypropylene (POP, Bsegment) were synthesized and they were reacted with polyoxypropylene his(6-aminohexyl) (POE) to enhance the hydrophilicity of the poly- mers. The degree of swelling of the POE -crosslinked block copolymers (CPB -2) was higher than that of the block dopolymers (PB). The amount of 5-fluorouracil re- leased from CPB-2 block copolymers was greater than that from the PB block copol- ymers when they were incubated in the same period. These results indicate that the amount of 5-fluorouracil released from the matrices is proportional to the hydrophilicity of the polymers. Observing polymer surfaces by scanning electron mi- croscope, pores (diameter ; $0.5-1.5{\mu}$m) were appeared on the surface of CPB-2

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RADIOAUTOGRAPHIC STUDY OF THE POSTNATAL DEVELOPMENT OF THE PALATE FOLLOWING 5-FLUOROURACIL ADMINISTRATION IN MICE (6-Fluorouracil이 핵서의 구개발육에 미치는 영향에 대한 자기방사법적 연구)

  • Nahm, Dong Seok
    • The korean journal of orthodontics
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    • v.5 no.1
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    • pp.43-50
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    • 1975
  • 항암화학요법제인 5-FUR이 백서의 구개발육에 미치는 영향을 연구코자 20수의 신생백서를 반씩 나누어 실험군에는 체중kg당 25mg의 동 약제를 2회 복강내 주사하고 대조군에는 생리적 식염수만을 주사한 후 제 1, 3, 7, 14 및 21일에 각각 2수씩 도살하였다. 또한 도살 2시간전에 체중 gm당 $5{\mu}Ci$$H^3-TDR$을 주사하여 자기방사법적으로 처리 관찰하였다. 결과는 다음과 같다. 1. labeling index는 실험일자의 경과에 따라 점차 감소하였다. 2. 5-FUR의 억제작용이 골아세포층과 경구개의 상피층에서 제 7일에 가장 강하게 나타났고 제 14일부터는 감소되는 경향을 나타내었다. 3. 연구개의상피층과 glandular gene에서는 5-FUH의 억제효과가 제 3일에 가장 심히 나타났으며 제 7일부터는 감소되었다. 4. 5-FUR의 억제효과는 점차 감소되어 제21일에는 대조군과의 차이가 현저히 감소하였다. 5. 골아세포층이 5-FUR의 영향을 가장 심하게 받는 반면에 그 회복도 가장 빨랐다.

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