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The receptor tyrosine kinase FLT3 is expressed almost exclusively in the hematopoietic compartment. Binding of its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. This leads to autophosphorylation of FLT3 on several tyrosine residues which constitute high affinity binding sites for signal transduction molecules. Recruitment of these signal t
Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes
Background: The Bone Scan Index (BSI) is used to quantitatively assess the total tumour burden in bone scans of patients with metastatic prostate cancer. The clinical utility of BSI has recently been validated as a prognostic imaging biomarker. However, the clinical utility of the on-treatment change in BSI is dependent on the reproducibility of bone scans. The objective of this prospective study
Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-
Background: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. Methods: In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres i
Purpose: The number of childbirths among cancer survivors continues to increase, but it is still largely unknown whether the children of cancer survivors might experience adverse health outcomes during the process of growing up. Methods: We identified all individuals diagnosed with cancer between 1958 and 2015 from the Swedish Cancer Registry and linked them to the Swedish Medical Birth Register t
Sepsis is a common and often deadly systemic response to an infection, usually caused by bacteria. The gold standard for finding the causing pathogen in a blood sample is blood culture, which may take hours to days. Shortening the time to diagnosis would significantly reduce mortality. To replace the time-consuming blood culture we are developing a method to directly separate bacteria from red and
Recent evidence suggests that cholera toxin might have multiple functions regarding the ability to regulate the immune system. However, it is unknown whether subsequent administration of cholera vaccine might affect the mortality rate in patients with prostate cancer. Here we report that patients in Sweden, who were diagnosed with prostate cancer between July 2005 and December 2014 and used choler
The exact physiological role for the monoamine serotonin (5-HT) in modulation of insulin secretion is yet to be fully understood. Although the presence of this monoamine in islets of Langerhans is well established, it is only with recent advances that the complex signaling network in islets involving 5-HT is being unraveled. With more than fourteen different 5-HT receptors expressed in human islet
Background: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke ris
Background & Aims Cholera toxin can act as a modulator of the immune response with anti-inflammatory effects; it reduces development of colon polyps in mouse models of colorectal cancer (CRC). We performed a population-based study to determine whether, in patients with a diagnosis of CRC, subsequent administration of the cholera vaccine (killed Vibrio cholerae O1 whole cells and recombinant ch
Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder wer
We performed genome-wide association studies and found single nucleotide polymorphisms (SNPs) at seven independent loci associated with prostate-cancer-specific survival time. Two SNPs replicated in an independent cohort. The SNP rs73055188 at AOX1 is associated with AOX1 gene expression level, which is correlated with biochemical recurrence.
At the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two-sample univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological subtypes based on an aggregated genome-wide assoc
Background: Testing for prostate-specific antigen (PSA) levels in blood are widely used and associated with prostate cancer risk and outcome. After puberty, PSA levels increase by age and multiple single nucleotide polymorphisms (SNPs) have been found to be associated with PSA levels. However, the relationship between the effects of SNPs and age on PSA remains unknown. Methods: To test for SNP × a
CVD and cancer are the two leading causes of death worldwide. Improvement in cancer early detection and treatment has resulted in an increased number of cancer survivors. However, many of the survivors tend to develop CVD often leading to their demise. Conversely, people with pre-existing CVD conditions, especially the elderly, have increased chances of developing cancer and dying from the same. T
It has been suggested that high intake of added sugar and sugar-sweetened beverages (SSBs) increase the level of circulating inflammatory proteins and that chronic inflammation plays a role in type 2 diabetes (T2D) development. We aim to examine how added sugar and SSB intake associate with 136 measured plasma proteins and C-reactive protein (CRP) in the Malmö Diet and Cancer-Cardiovascular Cohort
AIMS: The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality.METHODS AND RESULTS: Plasma samples from 1713 individuals from the Swedish population-bas
