Trifluorothymidine (TFT) is well known to be converted to TFT-monophosphate by thymidine kinase and to inhibit thymidylate synthase. In addition, TFT-triphosphate (TFT-TP) is also incorporated into DNA, resulting in cytocidal effects. However, the precise mechanism of TFT-induced DNA damage is still unclear. Therefore, we investigated the modes of action of TFT against DNA replication and repai...

The potential to reconstitute the whole erythropoiesis of a genetically anemic (WB x C57BL/6)F1-W/W (WBB6F1W/WV) mouse for at least 8 weeks was compared between 5-fluorouracil (5FU)-treated and nontreated bone marrow cells. C57BI/6 Pgk 1b/Pgk 1 female mice, in which each stem cell had either A-type or B-type phosphoglycerate kinase (PGK) owing to the random inactivation of one of two X chromoso...

Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and induc...

Yeast cytosine deaminase (yCD), a zinc metalloenzyme, catalyzes the hydrolytic deamination of cytosine to uracil. The enzyme is of great biomedical interest because it also catalyzes the deamination of the prodrug 5-fluorocytosine (5FC) to form the anticancer drug 5-fluorouracil (5FU). yCD/5FC is one of the most widely used enzyme/prodrug combinations for gene-directed enzyme prodrug therapy fo...

Oxaliplatin, established as a therapeutic standard globally for advanced/recurrent colorectal cancer, was approved in Japan in April 2005. With this approval the FOLFOX and FOLFIRI regimens are often selected now as 1st or 2nd line treatment for advanced/recurrent colorectal cancer. Patients receiving these regimens needed to be hospitalized, because the total treatment period was as long as 48...

–Pterygium is a fibrovascular proliferation of conjunctiva onto the cornea which leads to considerable visual impairment due to corneal astigmatism. Surgical excision is the only treatment; however recurrence continues to be a complication. Therefore, ant metabolites like Mitomycin C & 5Fluorouracil have been used as chemoadjuvant to reduce it. Present study was carried out to evaluate the effi...

We have used a lentiviral vector to stably express p53 at a physiological level in p53 knockout HCT116 cells. Cells transduced with wild type p53 responded to genotoxic stress by stabilizing p53 and expressing p53 target genes. The reconstituted cells underwent G(1) arrest or apoptosis appropriately depending on the type of stress, albeit less efficiently than parental wild type cells. Compared...

To investigate the mechanism of trifluorothymidine (TFT)-induced DNA damage, we developed an enzymatic method for the synthesis of single-strand oligonucleotides containing TFT-monophosphate residues. Sixteen-mer oligonucleotides and 14-mer 5'-phosphorylated oligonucleotides were annealed to the template of 25-mer, so as to empty one nucleotide site. TFT-triphosphate was incorporated into the s...

Nuclear magnetic resonance (NMR) spectroscopy has been used for structural characterization of 5-fluorouracil (5FU) & daunorubicin (DAU) co-loaded poly(butylcyanoacrylate) nanoparticles (PBCN), prepared by an anionic polymerization of n-butylcyanoacrylate, probing two different drug loading approaches. Diffusion ordered spectroscopy, obtained through pulsed field gradient NMR experiments, has b...