University of Milano-Bicocca

About: University of Milano-Bicocca is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Blood pressure. The organization has 8972 authors who have published 22322 publications receiving 620484 citations. The organization is also known as: Università degli Studi di Milano-Bicocca & Universita degli Studi di Milano-Bicocca.

BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells

Abstract: BRAF-activating mutations have been reported in several types of cancer, including melanoma ( approximately 70% of cases), thyroid (30-70%), ovarian (15-30%), and colorectal cancer (5-20%). Mutant BRAF has constitutive kinase activity and causes hyperactivation of the mitogen-activated protein kinase pathway. BRAF silencing induces regression of melanoma xenografts, indicating the essential role of BRAF for cell survival. We set up an inducible short hairpin RNA system to compare the role of oncogenic BRAF in thyroid carcinoma versus melanoma cells. Although BRAF knockdown led to apoptosis in the melanoma cell line A375, the anaplastic thyroid carcinoma cell ARO underwent growth arrest upon silencing, with little or no cell death. Reexpression of the thyroid differentiation marker, sodium iodide symporter, was induced after long-term silencing. The different outcome of BRAF down-regulation in the two cell lines was associated with an opposite regulation of p21(CIP1/WAF1) expression levels in response to the block of the BRAF mitogenic signal. These results were confirmed using a specific BRAF small-molecule inhibitor, PLX4032. Restoration of p21(CIP1/WAF1) expression rescued melanoma cells from death. Altogether, our data indicate that oncogenic BRAF inhibition can have a different effect on cell fate depending on the cellular type. Furthermore, we suggest that a BRAF-independent mechanism of cell survival exists in anaplastic thyroid cancer cells.

Repression of kit expression by Plzf in germ cells.

Abstract: Male mice lacking expression of Plzf, a DNA sequence-specific transcriptional repressor, show progressive germ cell depletion due to exhaustion of the spermatogonial stem cell population. This is likely due to the deregulated expression of genes controlling the switch between spermatogonial self-renewal and differentiation. Here we show that Plzf directly represses the transcription of kit, a hallmark of spermatogonial differentiation. Plzf represses both endogenous kit expression and expression of a reporter gene under the control of the kit promoter region. A discrete sequence of the kit promoter, required for Plzf-mediated kit transcriptional repression, is bound by Plzf both in vivo and in vitro. A 3-bp mutation in this Plzf binding site abolishes the responsiveness of the kit promoter to Plzf repression. A significant increase in kit expression is also found in the undifferentiated spermatogonia isolated from Plzf(-/-) mice. Thus, we suggest that one mechanism by which Plzf maintains the pool of spermatogonial stem cells is through a direct repression of kit expression.

Stroke mortality and trends from 1990 to 2006 in 39 countries from Europe and Central Asia: implications for control of high blood pressure.

Abstract: Aims The aim of the present study was to extend our understanding of international trends in stroke and major sequelae in Europe and countries peripheral to Europe by assessing: (1) current mortality rates, (2) the most recent 15-year prevalence trends, and (3) the relationship between systolic blood pressure in community surveys and national stroke mortality. Methods and results Data were obtained from the World Health Organization (WHO [www.who.int/whosis/database/mort/table.cfm][1]), and represent national vital statistics as reported by 39 countries (European and Central Asian countries) using a standard format and population-based cardiovascular surveys. Total numbers of deaths by stroke (International Classification of Diseases 430–438, 444) and the age, sex-adjusted incidence rates were obtained and grouped according to three standard demographic categories: A, B, and C (WHO). A Bayesian linear mixed effect model was fitted to the annual mortality rates. Higher rates of stroke mortality were observed for B and C group countries as compared with those countries belonging to Group A (e.g. Bulgaria 273.9 and 281.1; Israel 37.7 and 45.4 per 100 000 men and women, respectively). Even though the mortality rates within the country groupings were relatively similar, countries with marked deviation from the average were observed, mainly in Groups B and C. Stroke mortality decreased sharply in Group A during the period of study; conversely it had increased substantially in Group B and to a lesser extent in Group C. For both sexes markedly higher rates were noted moving from west to east, with some exceptions. Conclusion We have entered a period of rapidly increasing international inequality in stroke risk, where countries with low adult mortality in the latter 20th century extended their downward trend and countries with moderate as well as high mortality have on average seen unprecedented increases in death rates from stroke. [1]: http://www.who.int/whosis/database/mort/table.cfm

Self-report and clinician-rated measures of depression severity: can one replace the other?

Abstract: BACKGROUND: It has been suggested that clinician-rated scales and self-report questionnaires may be interchangeable in the measurement of depression severity, but it has not been tested whether clinically significant information is lost when assessment is restricted to either clinician-rated or self-report instruments. The aim of this study is to test whether self-report provides information relevant to short-term treatment outcomes that is not captured by clinician-rating and vice versa. METHODS: In genome-based drugs for depression (GENDEP), 811 patients with major depressive disorder treated with escitalopram or nortriptyline were assessed with the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Rating Scale for Depression (HRSD), and the self-report Beck Depression Inventory (BDI). In sequenced treatment alternatives to relieve depression (STAR*D), 4,041 patients treated with citalopram were assessed with the clinician-rated and self-report versions of the Quick Inventory of Depressive Symptomatology (QIDS-C and QIDS-SR) in addition to HRSD. RESULTS: In GENDEP, baseline BDI significantly predicted outcome on MADRS/HRSD after adjusting for baseline MADRS/HRSD, explaining additional 3 to 4% of variation in the clinician-rated outcomes (both P Language: en