Scirrhous cancer of the stomach which survived for more than five years after neoadjuvant chemotherapy with UFT (uracil and tegafur) and cisplatin.
(57/1786)
A 68-year-old man was diagnosed as having a scirrhous cancer of the stomach. Carcinomatous peritonitis was suspected on abdominal CT examination. Three courses of uracil and tegafur (UFT)/cisplatin (CDDP) chemotherapy were administered. The primary foci were reduced in size, then total gastrectomy was performed. Histological findings revealed a poorly differentiated adenocarcinoma with scirrhous invasion into the subserosa. Histological efficacy of the chemotherapy was judged to be grade 2. The patient has been alive without disease for more than five years after total gastrectomy. Neoadjuvant chemotherapy with UFT and CDDP may have contributed to the favorable clinical outcome in this patient. (+info)
Further studies of KMnO4 oxidation of synthetic DNAs containing oxidatively damaged bases.
(58/1786)
Recently we found that KMnO4 oxidation of DNA oligomers containing a 7,8-dihydro-8-oxoguanine (8-oxo-G) residue induces damage to the neighboring base residues; other modified bases, 7,8-dihydro-8-oxoadenine (8-oxo-A) and 5-hydroxyuracil (5-oh-U), show similar behavior in DNA. The present study indicated that the ability to induce damage, which could also occur by the oxidation of a 5-oh-C residue, was low as in the case of 5-oh-U. On the other hand, in order to examine the pathways and the intermediates for the oxidative degradation of 8-oxo-A, we have carried out the KMnO4 oxidation using an 8-oxo-2'-deoxyadenosine derivative as a model and have determined the structures of the three major products. (+info)
Photoreactivity of 5-iodouracil-containing DNA-Sso7d complex.
(59/1786)
X-ray structure of DNA-Sso7d complex indicated that binding of this protein causes sharp DNA bending. In order to examine whether this protein also causes DNA bending in solution, photoreactions of 1U-substituted DNA in the presence and the absence of Sso7d protein were investigated. It was found that the unusual intrastrand hydrogen abstraction at methyl of adjacent thymine occurred efficiently at the observed bending site of crystal structure. (+info)
Cellular repair mechanism of 5-formyluracil.
(60/1786)
5-Formyluracil (fU) is an oxidative DNA base damage. This damage has been suggested to be mutagenic and but enzymatic repair of the damage is little known. In this study, repair enzymes that recognize fU have been studied. Kinetic analysis of the repair activity of E. coli 3-methyladenine DNA glycosylase II (AlkA) showed that fU was removed by AlkA with the efficiency comparable to 7-methylguanine. We also examined the participation of the methyl-directed mismatch repair system. The affinity of MutS to the fU:G mispair was essentially similar to that of the T:G mispair that was most efficiently recognized by the MutSLH system. These results suggest two distinct repair pathways of fU in E. coli. (+info)
A method for the rapid preparation of 5-vinyluracil in high yield.
(61/1786)
A method for the rapid preparation of the thymineanalogue, 5-vinyluracil, in 83% yield from 5-(1-hydroxyethyl)uracil via the methanesulphonyl ester is reported. (+info)
Metabolism of pyrimidine bases and nucleosides in Neisseria meningitidis.
(62/1786)
In Neisseria meningitidis, uridine, deoxyuridine, cytosine, cytidine, or deoxycytidine could not be used by uracil-requiring mutants as pyrimidine sources. Consistent with these findings, only 5-fluorouracil of the different fluoropyrimidine bases and nucleosides showed any inhibitory effect on the growth of four prototrophic strains of N. meningitidis. Likewise, only radioactive uracil was readily incorporated into nucleic acids, whereas uptake of radioactive uridine, cytosine, or cytidine could not be demonstrated. Uracil was converted to uridine 5'-monophosphate by uracil phosphoribosyltransferase, whereas enzyme activities for conversion of cytosine or any of the nucleosides were not detectable in meningococcal extracts. (+info)
Comparative repair of the endogenous lesions 8-oxo-7, 8-dihydroguanine (8-oxoG), uracil and abasic site by mammalian cell extracts: 8-oxoG is poorly repaired by human cell extracts.
(63/1786)
The repair of the endogenous lesions 8-oxo-7,8-dihydroguanine (8-oxoG), uracil (U) and natural abasic site (AP site) was investigated using an in vitro base excision repair assay in which a plasmid substrate containing a single lesion at a defined position was repaired by mammalian cell extracts. Repair replication of an 8-oxoG/cytosine base pair performed by normal human cell extracts was approximately 5-fold less efficient than repair of a U/adenine base pair and, in turn, the latter was repaired approximately 10-fold less efficiently than an AP site placed in front of an adenine. A similar pattern of repair capacity for the three lesions was observed in Chinese hamster extracts. Repair of 8-oxoG was performed by the one nucleotide insertion pathway only. The lower repair replication ability of 8-oxoG with respect to U was linked to a lower DNA glycosylase (base removal) activity rather than to inability to process the beta-elimination cleaved strand left by the AP lyase activity associated with human oxoguanine DNA glycosylase 1. The data show that DNA repair of 8-oxoG is poor in human cells in comparison with other frequent endogenous lesions. (+info)
A multicenter phase II study of a five-day regimen of oral 5-fluorouracil plus eniluracil with or without leucovorin in patients with metastatic colorectal cancer.
(64/1786)
PURPOSE: To evaluate the safety and efficacy of a five-day regimen of oral 5-fluorouracil (5-FU) plus eniluracil (776C85) in patients with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Seventy-five patients with metastatic CRC that was previously untreated or refractory to 5-FU-leucovorin (LV) were enrolled and divided into two strata based upon their treatment history. Twenty-four had not previously received chemotherapy or had received adjuvant chemotherapy that ended > 6 months prior to enrollment on study (previously untreated stratum). Fifty-one patients had disease refractory to intravenous (i.v.) 5-FU-LV (previously treated stratum). All patients received seven consecutive daily doses of eniluracil (20 mg/day) with once daily oral 5-FU given on days 2-6, repeated every four weeks. One-half of the patients in each stratum also received 50 mg/day oral LV on days 2-6. The 5-FU dose was 25 mg/m2 when administered without LV and 20 mg/m2 when administered with LV. RESULTS: Partial response (PR) was noted in 2 of 12 patients receiving eniluracil-5-FU and in 3 of 12 patients receiving eniluracil-5-FU-LV in the previously untreated stratum. No responses were observed in the refractory disease stratum, however, 15 patients (30%) demonstrated stable disease over 2-18+ courses of therapy. Non-hematologic toxicities were mild; only 7% of patients experienced grade 3 diarrhea. Myelosuppression was frequent and dose limiting. Neutropenic sepsis was reported in 13.5% of patients. CONCLUSIONS: Eniluracil with 5-FU administered orally with or without LV on a five-day schedule is active and well tolerated when given as primary therapy to patients with metastatic CRC. (+info)