p53 mutations in classic and pleomorphic invasive lobular carcinoma of the breast

Contains fulltext : 110338.pdf (publisher's version ) (Open Access)BACKGROUND: p53 is a tumor suppressor that is frequently mutated in human cancers. Although alterations in p53 are common in breast cancer, few studies have specifically investigated TP53 mutations in the breast cancer subtype invasive lobular carcinoma (ILC). Recently reported conditional mouse models have indicated that functional p53 inactivation may play a role in ILC development and progression. Since reports on the detection of TP53 mutations in the relatively favorable classic and more aggressive pleomorphic variants of ILC (PILC) are rare and ambiguous, we performed a comprehensive analysis to determine the mutation status of TP53 in these breast cancer subtypes. METHODS: To increase our understanding of p53-mediated pathways and the roles they may play in the etiology of classic ILC and PILC, we investigated TP53 mutations and p53 accumulation in a cohort of 22 cases of classic and 19 cases of PILC by direct DNA sequencing and immunohistochemistry. RESULTS: We observed 11 potentially pathogenic TP53 mutations, of which three were detected in classic ILC (13.6%) and 8 in PILC (42.1%; p = 0.04). While p53 protein accumulation was not significantly different between classic and pleomorphic ILC, mutations that affected structure and protein function were significantly associated with p53 protein levels. CONCLUSION: TP53 mutations occur more frequently in PILC than classic ILC.1 april 201

Hydroxyl radical induced damage to the purine bases of DNA: in vitro studies

The hydroxyl (OH•) radical plays an important role in the degradation of living tissues induced by ionizing radiation. One of the main causes of this phenomenon are the chemical changes in the DNA bases produced by the reaction with this radical.A general comparison is made concerning the reaction of the OH• radical with the two purine bases of DNA. The results obtained for adenine and guanosine and their derivatives are based on time resolved studies (by pulse radiolysis with optical and conductance detection) of the primary radicals formed and their transformation reactions, and on identification (by HPLC with UV and electrochemical detection) of the corresponding final products.The OH• radical reacts with adenine and guanine (and also with their nucleosides, nucleotides and methylated derivatives) by addition to C(4), C(5) and C(S). The corresponding adducts undergo first order transformations, identified as dehydration and opening of the imidazole ring, which can be distinguished by their different activation parameters and sensitivity to acid-base catalysis. The resultant radicals are characterized by their different redox properties enabling the establishment of a mass balance that accounts quantitatively for the fate of the OH• radical.The analysis of stable products shows that some radicals are repaired to the parent compound and others lead to structurally modified products. The hydroxylation at C(S) is an example of the latter, and a biologically relevant phenomenon

VIS/NIR absorption spectra of positively charged oligo(phenylenevinylene)s and comparison with time-dependent density functional theory calculations

A combined experimental and theoretical study of the optical properties of positively charged unsubstituted and dialkoxy-substituted phenylenevinylene (PV) oligomers in solution is presented. Cations of PV oligomers were produced by irradiation of a solution with high-energy electron pulses. The optical absorption spectra were measured using time-resolved visible/near-infrared (VIS/NIR) spectroscopy in the range of 500-2100 nm (0.6-2.5 eV). The optical absorption spectra of positively charged PVs are compared with results from time-dependent density functional theory (TDDFT) calculations and previous semiempirical calculations. The experimental spectra of cations of partially dialkoxy-substituted PVs indicate the presence of a transition with a maximum below 0.6 eV. According to earlier semiempirical calculations, the energy of this transition exhibits an oscillating behavior as a function of the length of the oligomer. This was not observed experimentally. However, the monotonic decrease of the low-energy absorption band, as obtained from TDDFT calculations, is in agreement with the experimental findings