Damaged DNA Binding Protein 2 Plays a Role in Breast Cancer Cell Growth

The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER)-positive (MCF-7 and T47D), but not in ER-negative breast cancer (MDA-MB231 and SKBR3) or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold) higher in ER-positive than in ER-negative tumor samples (P = 0.0208) from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase). These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer

Codice penale e procedura penale e leggi complementari

Giuffrè editore, Milan

Codice penale e procedura penale e leggi complementari

Milano: Giuffrè (Italy

Age-dependent nerve cell loss in the brain of Sprague-Dawley rats: effect of long term acetyl-L-carnitine treatment.

The age dependent loss of nerve cells was investigated in 22 brain areas from young (3 month), adult (13 month) and old (25 month) Sprague-Dawley rats. As in previous studies, we observed an age-related neuronal loss primarily in the archicortex and in the hippocampus and in other subcortical structures (amigdaloid nucleus, pontine nuclei, cerebellar cortex). In sensory areas of cerebral cortex the neuronal loss was less marked. The effect of a 6 month treatment with acetyl-L-carnitine (ALCAR) on the number of nerve cells in the same brain areas was also investigated. ALCAR treatment began when the rats were aged 16 months. ALCAR treatment was able to counteract the age-dependent decrease in nerve cell number primarily in the temporal and occipital cortical areas, in the archicortex and hippocampus. The above findings suggest that long term ALCAR treatment may be effective in slowing down the age-related nerve cell loss in some rat brain areas

Transient cerebral ischemia in the rat: a study by nuclear magnetic resonance spectroscopy

The energy state and the levels of metabolites involved in the phospholipid turnover during and following a transient cerebral ischemia have been evaluated with the aids of 31P and 1H nuclear magnetic resonance spectroscopy. Ischemia was induced by electrocoagulation of vertebral arteries in combination with transient occlusion of both common carotid arteries. After 10-min ischemia, the brain energy charge and the levels of high-energy phosphates were reduced, whereas lactic acid levels had undergone an 8-fold increase. Sixty minutes after cerebral blood flow recovery, brain energy charge and levels of high-energy phosphates returned to basal values, whereas lactic acid levels remained persistingly elevated; an increase in phosphocreatine was also observed. At this same time, glycerolphosphorylcholine levels were found to be significantly reduced

Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-L-carnitine treatment.

By using fluorescence microscopy and microfluorimetric techniques, the effects of ageing and of 11 months acetyl-L-carnitine (ALCAR) treatment on lipofuscin deposition within the cytoplasm of pyramidal neurons of rat prefrontal cortex and hippocampus (CA3 field) were assessed. No lipofuscin autofluorescence was observed in the nerve cell bodies of neurons under study in young rats (3 months of age), but lipopigment had accumulated in the same nerve cells of senescent rats (22 months of age). ALCAR administration significantly reduced the accumulation of lipofuscin within pyramidal neurons of the brain areas examined

Multivariate data analysis in biochemistry: a new integrative approach to metabolic control in brain aging

Principal component anal. (PCA) allows one to obtain a quant. measure of the state of metab. as a whole. This method was applied to the study of energy metab. during the aging process and of the effect of a drug (acetyl-1-carnitine) on the aging brain