In this paper, we introduce a general design to construct fluorescence-switching probes by using conjugates of a fluorescent molecular rotor and protein specific ligands for the selective protein detection and real-time tracking of protein degradation in living cells. Upon the interaction of the ligand with the protein ligand-binding domain, the crowded surroundings restrict the bond rotation o...

The formation and persistence of methylated purines was determined in mice that received a single s.c. injection of 1,2-[14C]dimethylhydrazine (15 mg/kg) and were allowed to survive for 12 or 60 hr. In mice with a low susceptibility to dimethylhydrazine-induced colon carcinogenesis (C57BL/Ha), concentrations of 7-methylguanine and O6-methylguanine in DNA of colon, ileum, and kidney were 40 to 6...

The present study with N-methyl-N-nitrosounea and rat brain DNA was performed in order to study the distribution of alkyl ated products and the difference in the removal of these products from DNase I-sensitive and -resistant regions of DNA. Nuclei were isolated from N-[3H]methyb-N-nitnosourea-treated rats and incubated in the presence of DNase I (5 pg/mI). Digested DNA was further hydrolyzed i...

PURPOSE A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. EXPERIMENTAL DESIGN Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 m...

Gliomas are highly lethal neoplasms that cannot be cured by currently available therapies. Temozolomide is a recently introduced alkylating agent that has yielded a significant benefit in the treatment of high-grade gliomas. However, either de novo or acquired chemoresistance occurs frequently and has been attributed to increased levels of O6-methylguanine-DNA methyltransferase or to the loss o...

O(6)-Methylguanine and O(6)-chloroethylguanine, which are the primary cytotoxic DNA lesions produced by 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (dacarbazine) and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), respectively, can be repaired by O(6)-methylguanine-DNA methyltransferase (MGMT), coded by the MGMT gene. However, the two types of drugs exhib...

Single-stranded M13mp18 phage DNA was methylated with dimethylsulfate (DMS), and further treated with alkali to ring-open N7-methylguanine residues and yield 2-6-diamino-4-hydroxy-5N-methylformamidopyrimidine (Fapy) residues. Nucleotide incorporation during in vitro DNA synthesis on methylated template using E. coli DNA polymerase Klenow fragment (Kf polymerase) was reduced compared to the unme...

Rationale: Aggressive pituitary adenomas and pituitary carcinomas are rare and demand multiple treatment strategies. Temozolomide, an orally active alkylating chemotherapeutic agent, has recently been recommended as a salvage medication for refractory pituitary adenomas or carcinomas. Patient concerns: A 17-year-old male presenting with aggressive prolactinoma that continued to progress despite...

wnloaded ects in MLH1, as with other mismatch repair (MMR) proteins, are the primary cause of hereditary lyposis colon cancer (HNPCC). Mutations in MMR genes often disrupt mismatch repair and MMR ing functions. However, some HNPCC-associated mutations have unknown pathogenicity. Here, cover an MLH1 clinical mutation with a leucine (L)-to-histidine (H) amino acid change at position at ablates ML...

Clinical application of gene therapy for genetic and malignant diseases has been limited by inefficient stem cell gene transfer. Here we studied in a clinically relevant canine model whether genetic chemoprotection mediated by a mutant of the DNA-repair enzyme methylguanine methyltransferase could circumvent this limitation. We hypothesized that genetic chemoprotection might also be used to enh...