Search results for "Fluorou"

Artificial increase of uracilemia during fluoropyrimidine treatment can lead to DPD deficiency misinterpretation

2021

Each year in France, >75 000 patients receive fluoropyrimidines, including 5-fluorouracil (5-FU) and its oral prodrug capecitabine (Xeloda), to treat digestive, breast and head and neck cancers.1 Among them, ∼20% will experience severe hematological and digestive toxicities and <2% will have a fatal outcome in the first two cycles. A part of these toxicities may result from a deficiency in dihydropyrimidine dehydrogenase (DPD) which catabolizes the endogenous uracil (U) into dihydrouracil (UH2) as well as 5-FU. In 2018, French Health Authorities [Haute Autorité de Santé (HAS) and Institut National du Cancer, (INCa)] recommended the evaluation of the enzymatic activity of DPD by measuring th…

5-Fluorouracil Buccal Tablets for Locoregional Chemotherapy of Oral Squamous Cell Carcinoma: Formulation, Drug Release and Histological Effects on Re…

2010

5-Fluorouracil (5-FU) is currently used for treatment of oral squamous cell carcinoma (OSCC). 5-FU is given by i.v. although the systemic administration is associated with severe toxic effects and no topical formulations of 5-FU for buccal drug delivery have been reported. In this study we would report the development of buccal tablets suitable for direct application of low-doses of 5-FU on cancer lesions. The topical administration could be effective on tumor area while systemic undesired side effects are avoided. Preliminarily, the limited tendency of 5-FU to cross the buccal tissue was established using reconstituted human oral epithelium (RHOE, in vitro) and porcine buccal mucosa (ex vi…

Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three- Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile …

2012

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal …

The role of drug sequence in therapeutic selectivity of the combination of 5-fluorouracil and cis-platin.

1989

The therapeutic efficacy of 5-fluorouracil (FUra) and cis-dichlorodiamine-platinum (cis-DDP) in mice bearing transplantable leukemia and solid tumors was evaluated using different sequences of combination of these agents. The optimal sequence was cis-DDP administered 24 h after FUra. The administration of FUra at its maximally tolerated dose (MTD) followed 24 h later by low doses of cis-DDP yielded less toxicity and higher response rate against L1210 and colon 26 than the administration of these two agents in the opposite sequence or concurrently at the MTD. The sequence of administration of these two agents was not therapeutically important when the antitumor activity was evaluated against…

Effect of human granulocyte colony stimulating factor (G-CSF) and reduced glutathione (GSH) on drug-induced leukopenia in golden Syrian hamsters.

1990

Vinorelbine and 5-fluorouracil bolus and/or continuous venous infusion plus levofolinic acid as second-line chemotherapy for metastatic breast cancer…

2006

Background: This retrospective study evaluated the activity and toxicity profile of a regimen of vinorelbine and 5-fluorouracil with levofolinic acid, given to a large series of patients with recurrent or refractory metastatic breast cancer after first-line chemotherapy. Patients and Methods: Overall, 286 evaluable patients were included in the analysis. Two chemotherapy schedules were reviewed: a) the bolus regimen consisted of levofolinic acid 100 mg/m(2) and 5-fluorouracil 375 mg/m(2) both administered i.v. on days 1,2 and 3, plus vinorelbine 25 mg/m(2) i.v. bolus on days I and 8 every 3 weeks; b) the infusional regimen of levofolinic acid 100 mg/m(2) given as a 2-hour infusion, followed…

Direct experimental observation of mesoscopic fluorous domains in fluorinated room temperature ionic liquids

2017

Fluorinated room temperature ionic liquids (FRTILs) represent a class of solvent media that are attracting great attention due to their IL-specific properties as well as features stemming from their fluorous nature. Medium-to-long fluorous tails constitute a well-defined apolar moiety in the otherwise polar environment. Similarly to the case of alkyl tails, such chains are expected to result in the formation of self-assembled fluorous domains. So far, however, no direct experimental observation has been made of the existence of such structural heterogeneities on the nm scale. We report here the first experimental evidence of the existence of mesoscopic spatial segregation of fluorinated dom…

Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response

2009

Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC) samples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA str…

Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein

2008

To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML).The role of p53 and PML in regulating cytotoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Furthermore, H-1 PV infection was combined with cytostatic drug treatment.While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis, the cytotoxicity of H-1 PV was more pronounced in p53-negative than in p…

Immune effects of 5-fluorouracil

2012

Cytotoxic anticancer drugs can promote antitumor immune responses. The anticancer activity of 5-fluorouracil (5FU) relies on the restoration of T-cell immunity following the elimination of myeloid-derived suppressor cells (MDSCs). We have recently discovered that the 5FU-driven activation of the NLRP3 inflammasome in MDSCs promotes tumor angiogenesis by eliciting TH17 responses that compromise anticancer immunity. This underscores the need to combine 5-FU with NLRP3 inhibitors to prevent tumor progression.