SMJERNICE ZA DIJAGNOZU, ZDRAVSTVENIM STANJEM UVJETOVANU KVALITETUŽIVOTA I TERAPIJU KARCINOMA PROSTATE – PROTURJEČJA UROLOŠKE ONKOLOGIJE

Currently, it is recommended that prostate cancer be detected by digital rectal palpation and prostate specifi c antigen (PSA) elevation. TRUS coupled with ultrasound-guided biopsies might become the most appealing staging technique for early diagnosed prostate cancer. To promote earlier diagnosis, better PSA thresholds need to be defi ned, with a clear free- PSA threshold. This could be complemented by the use of nomograms and, in suspected cases, repeated biopsies, TRUS, bone scans and new imaging techniques. Deferred therapy by means of active observation and alertness to start therapy when signs of rapid progression occur may therefore be an alternative to active therapy in patients with low-risk localized prostate cancer with life expectancy of 10 years or less. Radical prostatectomy was more effective than watchful waiting in terms of cancer-specifi c survival benefi t, when compared in a prospective randomized trial. Neoadjuvant hormonal therapy has a nonsignifi cant impact on overall and progression free survival. In Europe, the focus is on biochemical recurrence after curative treatment (nerve sparing radical prostatectomy and/or radiotherapy in low-, intermediate- and high-risk patients with 72-78 Gy. In metastatic disease, adjuvant androgen deprivation is the treatment of choice. These are patients that cannot be cured. Identifi cation of intracellular androgen synthesis by prostate cancer cells has led to identifi cation of new targets, several novel strategies, third-generation drugs, inhibitors of androgen synthesis, more potent androgen receptor antagonists. Castration-resistant prostate cancer remains dependent on androgens and signaling through androgen receptor. Substantial pain reduction, improvement in PSA response and quality of life often make chemotherapy with docetaxel for hormone refractory prostate cancer better choice than simple pain and complication treatment. The main features of each condition and its management are summarized.Za rano otkrivanje karcinoma prostate danas se preporuča provesti digitorektalnu palpaciju te pratiti povišenje vrijednosti antigena specifi čnog za prostatu (PSA). Transrektalna ultrasonografi ja (TRUS) zajedno s ultrazvučno vođenim biopsijama mogla bi postati najprihvatljivija tehnika utvrđivanja stadija za rano otkrivene karcinome prostate. Kako bi se postigla ranija dijagnoza potrebno je bolje defi nirati granične vrijednosti za PSA s jasno iskazanom graničnom vrijednosti za slobodni PSA. Tome bi se moglo pridodati i korištenje nomograma te u suspektnim slučajevima ponovljenih biopsija, TRUS-a, koštanih skeniranja i novih slikovnih tehnika u dijagnostici. Terapija s odgodom u kojoj se koriste metode aktivne opservacije i spremnosti na započinjanje terapije čim se pojave znaci brze progresije bolesti mogla bi stoga biti alternativa aktivnoj terapiji u bolesnika s lokaliziranim karcinomom prostate niskoga rizika, očekivanoga životnog vijeka deset godina ili manje. Prospektivna nasumična istraživanja pokazala su da je radikalna prostatektomija učinkovitija nego praćenje i čekanje u pogledu doprinosa preživljavanju kod bolesnika oboljelih od karcinoma. Neoadjuvantna hormonska terapija nema značajan utjecaj na cjelokupno preživljenje, kao ni na preživljenje bez progresije bolesti. U Europi je fokus postavljen na biokemijski relaps bolesti nakon kurativnoga liječenja (poštedna radikalna prostatektomija i/ili radioterapija kod bolesnika niskoga, umjerenoga i visokog rizika sa 72-78 Gy). Adjuvantna androgena deprivacija je terapija izbora kod metastatskoga oblika bolesti, kod bolesnika koje nije moguće izliječiti. Identifi kacija unutarstanične androgene sinteze koju provode stanice karcinoma prostate dovela je do identifi kacije novih ciljeva te do nekoliko novih strategija i lijekova treće generacije: inhibitora androgene sinteze, potentnijih antagonista androgenih receptora. Karcinom prostate rezistentan na kastraciju ostaje ovisan o androgenima i signalizaciji putem androgenih receptora. Kemoterapija docetakselom u liječenju refraktornog karcinoma prostate postiže značajnije smanjenje boli, bolji odgovor PSA i bolju kvalitetu života u usporedbi s jednostavnim postupcima liječenja boli i komplikacija. Ovaj rad daje pregled ključnih obilježja pojedinih bolesti te načina njihovog liječenja

The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

Integrating sequence and structural biology with DAS.

BACKGROUND: The Distributed Annotation System (DAS) is a network protocol for exchanging biological data. It is frequently used to share annotations of genomes and protein sequence. RESULTS: Here we present several extensions to the current DAS 1.5 protocol. These provide new commands to share alignments, three dimensional molecular structure data, add the possibility for registration and discovery of DAS servers, and provide a convention how to provide different types of data plots. We present examples of web sites and applications that use the new extensions. We operate a public registry of DAS sources, which now includes entries for more than 250 distinct sources. CONCLUSION: Our DAS extensions are essential for the management of the growing number of services and exchange of diverse biological data sets. In addition the extensions allow new types of applications to be developed and scientific questions to be addressed. The registry of DAS sources is available at http://www.dasregistry.org.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

DASMI: exchanging, annotating and assessing molecular interaction data

Motivation: Ever increasing amounts of biological interaction data are being accumulated worldwide, but they are currently not readily accessible to the biologist at a single site. New techniques are required for retrieving, sharing and presenting data spread over the Internet

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Podbat: A Novel Genomic Tool Reveals Swr1-Independent H2A.Z Incorporation at Gene Coding Sequences through Epigenetic Meta-Analysis

Epigenetic regulation consists of a multitude of different modifications that determine active and inactive states of chromatin. Conditions such as cell differentiation or exposure to environmental stress require concerted changes in gene expression. To interpret epigenomics data, a spectrum of different interconnected datasets is needed, ranging from the genome sequence and positions of histones, together with their modifications and variants, to the transcriptional output of genomic regions. Here we present a tool, Podbat (Positioning database and analysis tool), that incorporates data from various sources and allows detailed dissection of the entire range of chromatin modifications simultaneously. Podbat can be used to analyze, visualize, store and share epigenomics data. Among other functions, Podbat allows data-driven determination of genome regions of differential protein occupancy or RNA expression using Hidden Markov Models. Comparisons between datasets are facilitated to enable the study of the comprehensive chromatin modification system simultaneously, irrespective of data-generating technique. Any organism with a sequenced genome can be accommodated. We exemplify the power of Podbat by reanalyzing all to-date published genome-wide data for the histone variant H2A.Z in fission yeast together with other histone marks and also phenotypic response data from several sources. This meta-analysis led to the unexpected finding of H2A.Z incorporation in the coding regions of genes encoding proteins involved in the regulation of meiosis and genotoxic stress responses. This incorporation was partly independent of the H2A.Z-incorporating remodeller Swr1. We verified an Swr1-independent role for H2A.Z following genotoxic stress in vivo. Podbat is open source software freely downloadable from www.podbat.org, distributed under the GNU LGPL license. User manuals, test data and instructions are available at the website, as well as a repository for third party–developed plug-in modules. Podbat requires Java version 1.6 or higher

New national and regional bryophyte records, 52

Marchantia paleacea is a new species for the Umbria Region and is rare in central and southern Italy. This record is in a Site of Community Importance (SCI) IT5220017 and a Special Area of Conservation (SAC) of the Natura 2000 EU-wide network due to the presence of the 7220* ‘Petrifying springs with tufa formation (Cratoneurion)’ Annexe I priority habitat. The particular environment, with a gorge and waterfall, created a very special microclimate that allowed the establishment of interesting liverworts and mosses

Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods