Expression and subcellular localization of the bromodomain-containing protein 7 is a prognostic biomarker in breast cancer

Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family. Previous studies suggest that BRD7 is predominantly localized in the nucleus, wherein it functions as a transcriptional regulator. Several lines of evidence imply a tumour suppressor function for BRD7. However, the importance of BRD7 in the pathogenesis of breast cancer is not well understood. We have investigated the expression, CpG island methylation and subcellular localization of BRD7 in breast cancer cell lines and clinical cases and thereby assessed its prognostic significance by correlating with clinical-pathological features and time-dependent clinical outcomes. We show that nuclear exclusion of BRD7 occurs commonly in breast cancer and is strongly associated with cases expressing wild-type p53. Moreover, clinical outcomes are significantly less favourable in cases with nuclear exclusion or loss of expression than those in which there is nuclear expression of BRD7. Methylation of the CpG island of BRD7 increases in breast cancer relative to normal breast tissue, but there is not an obvious correlation between methylation and reduced expression or between methylation and clinical outcomes. Overall, our results suggest that nuclear exclusion, rather than transcriptional silencing, is a common mechanism by which the tumour suppressor function of wild-type p53 is inhibited in breast cancer, and show that BRD7 is a promising candidate biomarker in breast cancer

Direct surgery for brainstem tumours [Asportazione chirurgica diretta dei tumori del tronco cerebrale].

No abstract availabl

Understanding antipsychotic non-classical prescriptions: a quantitative and qualitative approach.

AIMS: To date only a few studies investigated the clinical reasons supporting and explaining non-classical antipsychotic prescriptions. The present study was carried out to develop concepts which help understand this phenomenon in a natural setting, giving emphasis to views of clinicians according to quali - quantitative research methodologies. SUBJECTS: From the South-Verona Psychiatric Case Register all antipsychotic prescriptions issued during 2005 were extracted. Concurrent prescribing of two or more antipsychotics, prescribing antipsychotic drugs outside the licensed indications, and outside the licensed ranges of doses reported in the Italian National Formulary, were considered non-classical prescriptions. Reasons for non-classical prescriptions were collected by means of brainstorming sessions with clinicians. Non-classical prescriptions and the corresponding reasons were grouped according to whether they were "clinically sound" or "clinically not sound". RESULTS: During 2005 a total of 259 patients received 376 non-classical prescriptions. The most frequently reported reasons for non-classical prescribing were that prescriptions were inherited from another clinician with or without benefit, and that prescriptions were motivated by the need of reducing psychotic symptoms. More than 60% of these non-classical prescriptions were categorised as "clinically sound". Clinically not sound prescriptions were related with negative clinicians' views and opinions about the patient/clinician relationship. CONCLUSION: Clinically not sound prescriptions appeared just a reflection of a problematic doctor/patient relationship, where no individual treatment plan existed and psychiatric visits had the only goal of monitoring ongoing prescriptions

Transmission Electron Microscopy of Lipid Vesicles for Drug Delivery: Comparison between Positive and Negative Staining

Lipid-containing nanostructures, in the form of solid lipid nanoparticles or iron oxide nanoparticles (NPs) coated with a lipid shell, were used as case studies for assessing and optimizing staining for transmission electron microscopy structural and compositional characterization. These systems are of paramount importance as drug delivery systems or as bio-compatible contrast agents. In particular, we have treated the systems with a negative (phospshotungstic acid) or with a positive (osmium tetroxide) staining agent. For iron-oxide NPs coated with the lipid shell, negative staining was more efficient with respect to the positive one. Nevertheless, in particular cases the combination of the two staining procedures provided more complete morphological and compositional characterization of the particles

MOLECULAR CHARACTERIZATION OF COMMON VARIABLE IMMUNODEFICIENCY-RELATED LYMPHOMAS

Common variable immunodeficiency (CVI) patients are at high relative risk of developing non-Hodgkin lymphomas (NHL), mainly represented by B-lineage diffuse large cell lymphomas. The molecular pathogenesis and histogenesis of CVI-related NHL are poorly understood. We have thus attempted to provide a detailed molecular characterization of their histogenesis and pathogenesis. A panel of 5 CVI-related NHL was subjected to detailed analysis of histogenetic markers (mutations of immunoglobulin variable heavy chain-IgVH and of BCL-6 genes) acquired by B-cells at the time of germinal center transit. Somatic hypermutation of IgVH and BCL-6 genes occurred in 5/5 cases; in all cases, mutations were stable with no evidence of ongoing mutation processes. In 3/5 cases, the pattern of IgVH mutations was consistent with selection and stimulation of the tumor clone by antigen. To further clarify the pathogenesis, samples were tested for inactivation by promoter hypermethylation of the genes 0(6)-methylguanine-DNA-methyltransferase (MGMT) and glutathione S-transferase (GST) p1, which code for detoxifying enzymes, as well as of death-associated protein (DAP)-kinase, coding for a proapoptotic molecule. Promoter hypermethylation of MGMT, GSTp1 and DAP-kinase was detected in 2/5, 3/5 and 3/5 CVI-related NHL, respectively. Overall, these data indicate that: i) similarly to other immunodeficiency-related NHL, CVI-related NHL derive from germinal center-related B-cells, namely centrocytes or post-germinal center B-cells; ii) antigen stimulation and selection are involved in the development of at least a fraction of these cases; iii) hypermethylation of the MGMT, DAP-kinase and GSTp1 genes occurs at sustained frequencies in CVI-related NHL and may provide novel prognostic markers and therapeutic targets for the clinical management of these lymphomas