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Purpose: Gene expression profile was analyzed in 68 stage I and 15 borderline ovarian cancers to determine if different clinical features of stage I ovarian cancer such as histotype, grade, and survival are related to differential gene expression. Experimental Design:Tumors were obtained directly at surgery and immediately frozen in liquid nitrogen until analysis. Glass arrays containing 16,000 genes were used in a dual-color assay labeling protocol. Results: Unsupervised analysis identified eight major patient partitions, one of which was statistically associated to overall survival, grading, and histotype and another with grading and histotype. Supervised analysis allowed detection of gene profiles clearly associated to histotype or to degree of differentiation. No difference was found between borderline and grade 1tumors. As to recurrence, a subset of genes able to differentiate relapsers from nonrelapsers was identified. Among these, cyclin E and minichromosome maintenance protein 5 were found particularly relevant, as their expression was inversely correlated to progression-free survival (P = 0.00033 and 0.017, respectively). Conclusions: Specific molecular signatures define different histotypes and prognosis of stage I ovarian cancer. Mucinous and clear cells histotypes can be distinguished from the others regardless of tumor grade. Cyclin E and minichromosome maintenance protein 5, whose expression was found previously to be related to a bad prognosis of advanced ovarian cancer, appear to be potential prognostic markers in stage I ovarian cancer too, independent of other pathologic and clinical variables.

Background: P63 belongs to the 'p53 family' whose role in cancer progression has been recently revisited in light of the plethora of splicing variants that are generated. We analyzed the expression of the full-length TAp63 gene and its dominant-negative form DNp63 in ovarian cancer biopsies to correlate their expression with clinical outcome. Materials and methods:Real-time RT-PCR analysis was used to determine the levels of TAp63 and DNp63 in 83 stage I and in 86 stage III ovarian cancer biopsies and in seven human ovarian cancer cell.Results: TAp63 levels were comparable in stage I and stage III, but DNp63 levels increased 77-fold in stage III, independently of the p53 status. Patients with high DNp63 expression had the worst overall survival (OS); patients with a DNp63/TAp63 ratio >2 had a poor OS. Patients with a high DNp63/TAp63 ratio were those with a poor response to platinum-based therapy.Conclusions: Data indicate a role for DNp63 as a potential biomarker to predict patient's outcome and tumor progression in ovarian cancer. This would have particularly clinical relevance in ovarian cancer where the high rate of mortality reflects our lack of knowledge of molecular mechanisms underlying cell progression toward malignancy.

Soy and genistein at nutritional doses induce fat development in LFD-fed mice and adipogenesis in 3T3-L1 cells, with a mechanism that involves, at least in vitro, ERβ and is dependent on cell differentiation stage.

Objectives To evaluate drug consumption in the elderly aged 75 years or more living at home. Design Cross-sectional study. Setting Old-old (i.e., >75 y) people living in central Turin, a city in northern Italy. Participants Thirty-four general practitioners (GPs), with 50 or more old-old people in their patient list, randomly chosen among the GPs working in the Unità Socio-Sanitaria Locale I (Local Health Unit I) of Turin; 261 old-old people (135 men and 126 women) randomly selected from the practice records. Methods Data were collected by the GP through a structured questionnaire during an office visit and by a social worker in a home interview within 14 days of the GP visit GPs were asked to record every diagnosis and drug currently taken by the patient; social workers were trained in the administration of a structured questionnaire exploring sociodemographic variables, drug use (following the medication inventory strategy), disability, cognitive functions, and depressive symptoms. Results Nearly all subjects (95% of the women and 91% of the men) were taking at least 1 drug. The overall number of drugs recorded was 917 (47.1% for men and 52.9% for women), of which 172 (18.8%) were not reported by the GP but were recorded during the social worker's visit. The mean number of drugs was 3.2 for men and 3.8 for women, with a statistically significant difference (p = 0.02), while the mean number of diagnoses was 2.3 and 2.6, respectively. The study of correlates of drug consumption showed a strong association with number of diagnoses at univariate analysis (p < 0.0001, with a linear correlation coefficient of 0.64). No multivariate model showed a clear superiority over the simple one containing only the number of diagnoses in predicting the total number of drugs taken. Cardiovascular, nervous system, and alimentary tract drugs were the most frequently used. A total of 107 subjects (41%) were taking at least 1 unreported drug. Conclusions Our study shows high drug consumption among old-old people, with nearly 20% of drugs taken not reported by the GP. These results emphasize the need for an essential therapeutic approach in old-old people, prescribing only drugs of scientifically proven efficacy. Furthermore, the GP must make more effort when collecting a drug history from old-old patients.

The p73 gene has a complex regulation, which leads to the expression of different isoforms, often with opposite biological effects. We have generated in the human colocarcinoma cell line HCT116, expressing a wild-type p53, an inducible DNp73a expressing system. Two clones (HCT116/DN3 and HCT116/DN14), upon doxycycline addition, show a strong expression of DNp73a. In vitro the two DNp73a overexpressing clones grow at similar rate of the control transfected clone (HCT116/8a) and similarly respond to DNA damage. When injected in mice, HCT116/DN3, HCT116/DN14, and HCT116/8a cells grew similarly in the absence or presence of tetracycline. In HCT116/DN3 and HCT116/DN14 tumors, tetracycline induced a strong expression of DNp73a both as mRNA and protein. These results indicate that in this system the overexpression of the DNp73a does not induce a more aggressive phenotype and does not seem to be associated with a reduced response of the cells to treatment with anticancer agents.

The p53 gene has been investigated for its role in epithelial ovarian cancer but data collected until now are contradictory. The evidence that p53 belongs with p63 and p73 to a family of transcription factors re-opened interest in this gene family.Here, we used quantitative real time RT-PCR to determine expression levels of TAp53, TAp73 and their N-terminal splice variants in a cohort of 169 ovarian cancer patients with stage I and stage III disease. The TAp73 levels in stage III biopsies differed by 100-fold depending on the p53 status and overall survival appears to be significantly related to ΔNp73 expression. Kaplan-Meyer analyses did not suggest a correlation between overall survival and levels of TAp73, ΔNp73 or the ΔNp73/TAp73 ratio. In conclusion, these data suggest that at least in our patient cohort p53 and p73 expression levels are not correlated to malignant progression of ovarian cancer. They might, however, play a role in tumour initiation.

Vascular endothelial growth factor