Search for Early Pancreatic Cancer Blood Biomarkers in Five European Prospective Population Biobanks Using Metabolomics

Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreati

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Plant biotechnology for deeper understanding, wider use and further development of agricultural and horticultural crops

Plants bind solar energy to organic matter via photosynthesis and assimilation of carbon dioxide from the atmosphere and comprise the major source of nutrition and bioenergy. Plant biotechnology contributes to solution of important constraints in food and feed production and creates new technologies and applications for the sustainable use of plant resources. Genome-wide approaches such as massive parallel sequencing and microarrays to study gene expression, molecular markers for selection of important traits in breeding, characterization of genetic diversity with the aforementioned approaches, and somatic hybridization and genetic transformation are important tools in plant biotechnology. In this paper, studies carried out on enhanced resistance to viruses and tolerance of cold stress in potato, genetic modification of flower pigmentation and morphology in gerbera, production of edible vaccines in transgenic barley seeds, and expression of heterologous proteins for pharmaceutical purposes from vector viruses were chosen to exemplify the general utility of biotechnological approaches and also how plant biotechnology research has developed on cultivated plants at University of Helsinki. The studies reveal cellular and genetic mechanisms and provide scientific information that can be used for widening the uses of crop plants. They can also be used to detect any putative risks associated with the use of the biotechnological application in agriculture and horticulture and to develop practises which reduce any inadvertent negative consequences that plant production may have to the environment.;Yhteyttävät kasvit ovat ravinnon ja bioenergian ensisijainenlähde maapallolla. Viljelykasvien ominaisuuksia muokkaamalla sekä kasvien biosynteesikoneistoa eri tavoin hyödyntämällä pyritään vastaamaan haasteisiin, joita väestönkasvu ja sen myötä lisääntyvä energian sekä ravinnon tarve tuovat ihmiskunnalle. Lisäksi on pyrittävä hillitsemään ilmastonmuutosta. Tämän katsauksen tarkoituksena on osoittaa, kuinka kasvibioteknologia auttaa vastaamaan näihin haasteisiin. Esimerkkeinä käytetään mm. perunan jalostukseen, viruskestävyyteen ja kylmyydensietoon sekä sädelatvan (gerberan) kukankehitykseen ja kukintaan kohdistuvaa bioteknologista tutkimusta. Se on tuottanut tietoa tärkeiden kasvigeenien sijainnista ja rakenteesta kasvigenomeissa, geenien säätelystä kehityksen aikana sekä geenien reagoinnista ympäristön muutoksiin ja taudinaiheuttajien tartuntaan. Näitä tietoja tarvitaan, jotta kasvien tuottavuutta ja kasvituotteiden laatua voidaan entisestään parantaa mm. biotekniikan keinoin. Molekyyligeneettiset tutkimukset tuottavat myös geenimerkkejä, joilla voidaan tehostaa perinteistä risteytysjalostusta. Geenitekniikan avulla on voitu kehittää uusia viruskestävyyden mekanismeja kasveihin. Biotekniikan menetelmiä voidaan hyödyntää myös syötävien rokotteiden tuottamiseen sekä farmasianteollisuuden tarvitsemien proteiinien tuotantoon kasveissa. Toisaalta biotekniikan menetelmiä tarvitaan geenivarojen kartoittamiseen sekä geneettisen monimuotoisuuden ja geenivirtojen selvittämiseen kasvipopulaatioissa. Näillä tutkimuksilla on merkitystä niin kasvien geenivarojen hyödyntämiselle kuin riskien tunnistamiselle sekä sellaisten viljelykäytäntöjen kehittämiselle, joilla voidaan ehkäistä maa- ja puutarhatalouden haittavaikutuksia viljely- ympäristön ulkopuolella. Tulevaisuudessa kasvibiotekniikalla nähdään entistä suurempi merkitys haettaessa ratkaisuja suuriin haasteisiin, jotka liittyvät ihmiskunnan selviytymiseen. Tähän tarvitaan kasvibiotekniikan osaamisen kartuttamista myös kehitysmaissa

Surgical treatment of locally advanced, non-metastatic, gastrointestinal stromal tumours after treatment with imatinib

Item does not contain fulltextAIMS: Patients with locally advanced gastrointestinal stromal tumours (GISTs) have a high risk of tumour perforation, incomplete tumour resections and often require multivisceral resections. Long-term disease-free and overall survival is usually impaired in this group of patients. Induction therapy with imatinib followed by surgery seems to be beneficial in terms of improved surgical results and long-term outcome. We report on a large cohort of locally advanced GIST patients who have been treated in four centres in the Netherlands specialized in the treatment of sarcomas. METHODS: Between August 2001 and June 2011, 57 patients underwent surgery for locally advanced GISTs after imatinib treatment. Data of all patients were retrospectively collected. Endpoints were progression-free and overall survival. RESULTS: The patients underwent surgery after a median of 8 (range 1-55) months of imatinib treatment. Median tumour size before treatment was 12.2 (range 5.2-30) cm and reduced to 6.2 (range 1-20) cm before surgery. No tumour perforation occurred and a surgical complete (R0) resection was achieved in 48 (84%) patients. Five-year PFS and OS were 77% and 88%. Eight patients had recurrent/metastatic disease. CONCLUSIONS: Imatinib in locally advanced GIST is feasible and enables a high complete resection rate without tumour rupture. The combination of imatinib and surgery in patients with locally advanced GIST seems to improve PFS and OS