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We explore cell heterogeneity during spontaneous and transcription-factor-driven commitment for network inference in hematopoiesis. Since individual genes display discrete OFF states or a distribution of ON levels, we compute and combine pairwise gene associations from binary and continuous components of gene expression in single cells. Ddit3 emerges as a regulatory node with positive linkage to e
Breast cancer (BC) is one of the leading causes of death among women worldwide. Immunostimulatory treatment has increasingly been used as adjuvant therapy in the last few years, in patients with melanoma and other cancer forms, often with an induction of autoimmunity as a consequence of a successful treatment. We aimed at investigating if coexisting autoimmune diseases (AD) or hypersensitivities (
Angiogenesis is one of the hallmarks of breast cancer. The status of angiogenesis is important in therapy choice. Spider telangiectasias (telangiectasias) may reflect an increased ability to form vessels. Our first aim was to identify patient and tumor characteristics associated with the occurrence of telangiectasias at the time of breast cancer diagnosis. The second aim was to study the overall s
The proto-oncogene SKI is highly expressed in human myeloid leukemia and also in murine hematopoietic stem cells. However, its operative relevance in these cells remains elusive. We have over-expressed SKI to define its intrinsic role in hematopoiesis and myeloid neoplasms, which resulted in a robust competitive advantage upon transplantation, a complete dominance of the stem and progenitor compar
Background. Multidisciplinary team (MDT) conferences have been introduced into standard cancer care, though evidence that it benefits the patient is weak. We used the national Swedish Rectal Cancer Register to evaluate predictors for case discussion at a MDT conference and its impact on treatment. Material and methods. Of the 6760 patients diagnosed with rectal cancer in Sweden between 2007 and 20
Transplantation of hematopoietic stem cells (HSCs) to treat hematological disorders is routinely used in the clinic. However, HSC therapy is hindered by the requirement of finding HLA-matched donors, as well as attaining sufficient numbers of long-term HSCs in the graft. Therefore, ex vivo expansion of transplantable HSC remains one of the "holy grails" of hematology. Without the ability to mainta
Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced
Improved outcome after rectal cancer surgery requires identification of novel risk factors of tumour recurrence in order to personalise therapy, that is, enhanced selection of high-risk patients to additional radiochemotherapy or intensified follow-up. In several tumour types, including colorectal cancer, high expression of the membrane-cytoskeleton linker ezrin has been suggested to impair progno
High levels of insulin-like growth factor-1 (IGF-1) have been associated with increased risk of developing several types of cancer including breast cancer. A set of nine haplotype tagging SNPs (htSNPs) in the IGF1 gene were associated with IGF-1 levels and prostate cancer in a Swedish population. We aimed to study the nine htSNPs in three haplotype blocks (block1: rs855211, rs35765, rs2162679; blo
Possibilities to undergo predictive genetic testing for cancer have expanded, which implies that an increasing number of healthy individuals will learn about cancer predisposition. Knowledge about how an increased risk of disease influences life in a long-term perspective is largely unknown, which led us to explore lived experiences in healthy mutation carriers with Lynch syndrome. Individual inte
Background We investigated whether prediagnostic reported intake of dairy products and dietary calcium are associated with colorectal cancer (CRC) survival. Methods Data from 3,859 subjects with CRC (42.1% male, mean age at diagnosis 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition (EPIC) cohort were analyzed. Intake of dairy products and dietary calcium was assessed at ba
The transcription factor interferon regulatory factor-8 (IRF8) is highly expressed in myeloid progenitors, while most myeloid leukemias show low or absent expression. Loss of IRF8 in mice leads to a myeloproliferative disorder, indicating a tumor-suppressive role of IRF8. The Wilms tumor gene 1 (WT1) protein represses the IRF8-promoter. The zinc finger protein ZNF224 can act as a transcriptional c
We used the paradigmatic GATA-PU.1 axis to explore, at the systems level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIP-seq of GATA1, GATA2, and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (1) differential complexity
Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) sy
BACKGROUND: Chemotherapy before resection of colorectal metastases in the liver is extensively used and has been shown to induce histopathological changes in the liver parenchyma, although little is known about the effect of chemotherapy on liver regeneration. The aim of this study was to determine if pre-operative chemotherapy influences the regenerated liver volume after a major liver resection.
Most individuals who learn about hereditary cancer manage well, but identification of subgroups who find this knowledge burdening would allow psychosocial intervention. The objective of the study was to assess sense of coherence (SOC) in individuals with Lynch syndrome with comparison to a general population and correlation to self-concept.
Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive b
The Emissions Trading Scheme represents a new departure in the field of environmental policy-making in the EU. With it, the EU has deployed a market-based instrument to meet its Kyoto Carbon Dioxide emissions reduction commitments. This paper will account for its emergence as a concrete policy output. It will first refer to the historical, ideational and interest-based logics which shaped its emer
Written declarations in the European Parliament have not been given much attention in the field of political science. The scope of this Master's thesis is to examine whether symbolic politics are present in written declarations and how this may show. In this study, the aspects of symbolic politics of written declarations of the sixth parliamentary term are examined using a taxonomy for id
The advent of Java and similar languages on the real-time system scene necessitates the development of efficient strategies for scheduling the work of a garbage collector in a non-intrusive way. We propose a scheduling strategy, time-triggered garbage collection, based on assigning the collector a deadline for when it must complete its current cycle. We show that a time-triggered CC with fixed dea
