Properties and units in the clinical laboratory sciences part XXIV. Properties and units in clinical molecular genetics (IUPAC Technical Report)

This document describes the application of the syntax, semantic rules, and format of the Nomenclature for Properties and Units (NPU) terminology for coded dedicated kinds-of-property in the subject field of clinical molecular genetics. A vocabulary for NPU definitions in this field, based on international terminology and nomenclature, is introduced and examples of actual NPU definitions for different types of investigations are given and explained

Regulatory Proteins in Progenitors and Differentiated Cells of the Human Prostate

Prostate cancer (PC) develops from an androgen-dependent tissue that contains androgen receptors in both the stromal and glandular compartments. Surgical removal of the prostate may cure the patient, but if metastatic spread has occurred, androgen suppression therapy is the standard treatment. However, most men will eventually fail this therapy and develop recurrent androgen-independent disease, for which there is no effective therapy. Our understanding of PC, including cell source and mechanisms in initiation and progression of PC, is impeded by our lack of knowledge regarding cell regulation, self-renewal, and cellular differentiation mechanisms in the prostate gland. In this study, we aimed to investigate these processes in the adult human prostate, by investigating localization, activity, and regulation of growth and differentiation modulating proteins in mature and differentiating cells of the adult prostate, including the benign and malignant prostate. In this thesis, I provide evidence for epithelial renewal in response to prostate tissue culture, and for basal and epithelial stem cell (SC) recruitment leading to an expansion of differentiating glandular precursor cells, and report the identification of several novel candidate epithelial SC-antigens in the prostate, including the putative suppressor of differentiation Dlk-1. We also supply evidence that nuclear Notch-1 activity down-regulates the candidate SC marker Dlk-1 in differentiating glandular precursor cells, that Notch-signalling regulates proliferation of precursor cells, and that inactive Notch-1 is a marker of mature glandular cells in the prostate. In addition, the identification of rare Dlk-1 expressing neuroendocrine cells suggests the existence of a common prostate epithelial progenitor, and a late precursor phenotype to this cell lineage. Data further suggest that stem cell factor (SCF) regulates prostate SC/progenitor biology through KIT-receptors, and the existence of a novel stromal progenitor phenotype in the prostate. We further show that the inhibitory peptide somatostatin (SS) is expressed in the prostate epithelial and mesenchymal SC/progenitor niche, and that SS regulates expansion of immature epithelia in primary prostate cell cultures, and that specific SS-receptors are up-regulated in PC. New therapeutics may be based on inhibitors/agonists of critical SC/niche and precursor cell signalling and differentiation-modulating molecules, or of their receptors; current results may set the stage for the development of new therapies in prostate glandular and stromal diseases

Överprövning inom offentlig upphandling

Alla statliga och kommunala myndigheter i Sverige är skyldiga att följa Lag (2007:1091) om offentlig upphandling (LOU) vid inköp av varor och tjänster. Offentlig upphandling omfattar mellan 15.5 och 18.5 procent av Sveriges BNP och det är således viktigt att upphandlingen går rätt till. Upphandling inom LOU är omfattande och görs i många steg. Förfrågningsunderlag ska skrivas, upphandlingen ska annonseras, anbud ska utvärderas, leverantörer ska uteslutas och till sist ska tilldelningsbeslut meddelas. I de fall då en leverantör tycker att de borde vunnit upphandlingen eller är missnöjd med de krav som ställts kan de överpröva upphandlingen, alternativt ansöka om skadestånd En överprövning kan leda till att upphandlingsunderlaget måste ändras eller att hela upphandlingen får göras om och överprövningsprocesser är ofta både är kostsamma och tidskrävande för upphandlande myndighet. I juli 2010 gjordes förändringar i LOU till följd av ett EU-direktiv som fick konsekvensen att antalet överprövningar i förvaltningsdomstolen ökat markant. Offentlig upphandling är ett omdebatterat ämne. Många argumenterar för att LOU borde avskaffas då upphandlingarna skulle fungera bättre om det inte fanns så många regler att följa. Andra argumenterar för att lagen är bra som den är idag och att den motverkar orättvisor och korruption. Den statistik som framställs är inte alltid rättvisande. Detta till trots är det ingen tvekan om att båda parter i upphandlingsprocessen till stor del är missnöjda med hur LOU påverkar upphandlingarna. Den stora frågan är hur situationen på bästa sätt skulle kunna förbättras för samtliga parter. Många lösningsförslag på hur överprövningar kan motverkas får till följd att LOUs ursprungliga syfte tar skada. Exempel på detta är att öka beloppet för direktupphandling samt att införa en avgift som den leverantör som överprövar måste betala, vilket till stor del skulle ha en negativ inverkan på de mindre företagen. Då LOU finns till för att ingen ska kunna behandlas orättvist och för att säkerställa att den leverantör som har det bästa anbudet vinner upphandlingen är dessa lösningar inte att rekommendera. För att minska antalet överprövningar utan att gå emot syftet med LOU kan en tidsfrist för de olika delarna av upphandlingen införas. Det skulle förhindra möjligheten att överpröva en felaktighet i anbudet i slutet av en upphandling. Ett annat förslag är att samla alla upphandlingsmål till en och samma domstol. Detta skulle leda till bättre kompetens och snabbare handläggning samtidigt som det inte skulle finnas lika mycket spretigt praxis där domstolar dömt liknande fall olika

Targeting prostate cancer stem cells with alpha-particle therapy

Modern molecular and radiopharmaceutical development has brought the promise of tumor-selective delivery of antibody-drug conjugates to tumor cells for the diagnosis and treatment of primary and disseminated tumor disease. The classical mode of discourse regarding targeted therapy has been that the antigen targeted must be highly and homogenously expressed in the tumor cell population, and at the same time exhibit low expression in healthy tissue. However, there is increasing evidence that the reason cancer patients are not cured by current protocols is that there exist subpopulations of cancer cells that are resistant to conventional therapy including radioresistance and that these cells express other target antigens than the bulk of the tumor cells. These types of cells are often referred to as cancer stem cells (CSCs). The CSCs are tumorigenic and have the ability to give rise to all types of cells found in a cancerous disease through the processes of self-renewal and differentiation. If the CSCs are not eradicated, the cancer is likely to recur after therapy. Due to some of the characteristics of alpha particles, such as short path length and high density of energy depositions per distance traveled in tissue, they are especially well suited for use in targeted therapies against microscopic cancerous disease. The characteristics of alpha particles further make it possible to minimize the irradiation of non-targeted surrounding healthy tissue, but most importantly, make it possible to deliver high-absorbed doses locally and therefore eradicating small tumor cell clusters on the submillimeter level, or even single tumor cells. When alpha particles pass through a cell, they cause severe damage to the cell membrane, cytoplasm, and nucleus, including double-strand breaks of DNA that are very difficult to repair for the cell. This means that very few hits to a cell by alpha particles are needed in order to cause cell death, enabling killing of cells, such as CSCs, exhibiting cellular resistance mechanisms to conventional therapy. This paper presents and evaluates the possibility of using alpha-particle emitting radionuclides in the treatment of prostate cancer (PCa) and discusses the parameters that have to be considered as well as pros and cons of targeted alpha-particle therapy in the treatment of PCa. By targeting and eradicating the CSCs responsible of tumor recurrence in patients who no longer respond to conventional therapies, including androgen deprivation and castration, it may be possible to cure the disease, or prolong survival significantly. © 2017 Ceder and Elgqvist

Neuroendocrine Mediators in Prostate Cancer Progression

Recent years have seen a number of exciting developments in the evolving and expanding role of somatostatin and its analog, octreotide, in the diagnosis and treatment of cancer. It is now clear that octreotide has potential applications not just in imaging, but also in medical therapy and radiotherapy. This book contains the papers from a symposium held in September 2001 in Noordwijk in The Netherlands where all of these varied aspects of the expanding role of octreotide in clinical oncology were discussed