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Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 1

Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting

Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44–73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow-up, and body mass index

Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

During development, hematopoietic stem and progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we dem

Intake of different types of red meat, poultry, and fish and incident colorectal cancer in women and men: results from the Malmö Diet and Cancer Study.

Background : Colorectal cancer (CRC) is considered one of the most common forms of cancer in the Western world. High intake of red and processed meat is considered to increase CRC development. Objective : This study examined associations between intake of red meats, poultry, and fish and incident CRC, and if weight status modifies the associations. Design : In the Malmö Diet and Cancer Study, diet

Understanding and Modulating Immunity With Cell Reprogramming

Cell reprogramming concepts have been classically developed in the fields of developmental and stem cell biology and are currently being explored for regenerative medicine, given its potential to generate desired cell types for replacement therapy. Cell fate can be experimentally reversed or modified by enforced expression of lineage specific transcription factors leading to pluripotency or attain

Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells

Adhesion is a key component of hematopoietic stem cell regulation mediating homing and retention to the niche in the bone marrow. Here, using an RNA interference screen, we identify cytohesin 1 (CYTH1) as a critical mediator of adhesive properties in primary human cord blood-derived hematopoietic stem and progenitor cells (HSPCs). Knockdown of CYTH1 disrupted adhesion of HSPCs to primary human mes

Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) dat

Evaluation of reproducibility in MRI quantitative volumetric assessment and its role in the prediction of overall survival and progression-free survival in glioblastoma

Background: Residual tumor volume (RTV) and extent of resection (EOR) have previously been shown to affect survival in glioblastoma (GB) patients. Quantitative radiological assessment (QRA) of these factors could potentially affect clinical decision-making in the postoperative period. Purpose: The first aim was to evaluate the reproducibility of different volume estimation methods of RTV and EOR b

TCF7L2 type 2 diabetes risk variant, lifestyle factors, and incidence of prostate cancer.

Variation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2 diabetes (T2D), may play a role in prostate cancer (PCa) depending on lifestyle factors. The aims of this study were to determine if TCF7L2 rs7903146 is associated with risk of PCa and if the association is modified by lifestyle factors independently of T2D status.

miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients.

Background:The microRNA-205 (miR-205) has been shown to be deregulated in prostate cancer (PCa). Here we continue to investigate the prognostic and therapeutic potential of this microRNA.Methods:The expression of miR-205 is measured by qRT-PCR and in situ hybridisation in a well-documented PCa cohort. An AGO2-based RIP-Chip assay is used to identify targets that are verified with western blots, lu

HIF-1α can act as a tumor suppressor gene in murine Acute Myeloid Leukemia.

Self-renewal of hematopoietic stem cells (HSCs) and leukemia-initiating cells (LICs) has been proposed to be influenced by low oxygen tension (hypoxia). This signaling, related to the cellular localization inside the bone marrow niche and/or influenced by extrinsic factors, promotes the stabilization of hypoxia inducible factors (HIFs). Whether HIF-1α can be used as a therapeutic target in the tre

Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation

Acquisition of homozygous activating growth factor receptor mutations might accelerate cancer progression through a simple gene-dosage effect. Internal tandem duplications (ITDs) of FLT3 occur in approximately 25% cases of acute myeloid leukemia and induce ligand-independent constitutive signaling. Homozygous FLT3-ITDs confer an adverse prognosis and are frequently detected at relapse. Using a mou

Molecular microheterogeneity of prostate specific antigen in seminal fluid by mass spectrometry.

OBJECTIVES: Prostate specific antigen (PSA) is a widely used and clinically valuable marker for prostate disease. In order to enable the development of new PSA assays and progress the understanding of the biology of PSA we have analyzed PSA in seminal plasma. Design and methods PSA in seminal plasma from men attending a fertility clinic and healthy controls was analyzed using SDS-PAGE, Western blo

Glucocorticoids improve erythroid progenitor maintenance and dampen Trp53 response in a mouse model of Diamond-Blackfan anaemia.

Diamond-Blackfan anaemia (DBA) is a rare congenital disease causing severe anaemia and progressive bone marrow failure. The majority of patients carry mutations in ribosomal proteins, which leads to depletion of erythroid progenitors in the bone marrow. As many as 40% of all DBA patients receive glucocorticoids to alleviate their anaemia. However, despite their use in DBA treatment for more than h

Challenges in teaching international students: group separation, language barriers and culture differences

Every year, there are more than 2500 new international students coming to Lund University and starting their higher education path. A higher number of foreign students increased the international competitiveness of Lund University, but at the same time the international students had to face many problems for instance, culture shock and language barriers. In this report we focused on issues in teac

Shortened constraint-induced movement therapy in subacute stroke - No effect of using a restraint: A randomized controlled study with independent observers.

OBJECTIVE: To examine the effect of using a mitt during shortened constraint-induced movement therapy for patients in the subacute phase after stroke. SUBJECTS: Twenty-four patients with stroke (mean age 57.6 (standard deviation (SD) 8.5) years; average 7 weeks post-stroke) with mild to moderate impaired hand function. METHODS: The patients were randomized to mitt use or no mitt use on the less af

Male infertility and prostate cancer risk: a nested case-control study.

The pathogenesis of prostate cancer is unclear, although experimental evidence implicates androgens as playing an important role. Infertile men frequently suffer from some degree of hypogonadism and may hence be hypothesized to be at lower risk of developing prostate cancer than fertile men. To test this hypothesis, we conducted a case-control study nested within "the Malmö Diet and Cancer Study"

SMAD4 binds HOXA9 in the cytoplasm and protects primitive hematopoietic cells against nuclear activation by HOXA9 and leukemia transformation.

We studied leukemic stem cells (LSCs) in a Smad4(-/-) mouse model of acute myelogenous leukemia (AML) induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9. While HOXA9-SMAD4 complexes accumulate in the cytoplasm of normal hematopoietic stem- and progenitor cells (HSPCs) transduced with these oncogenes, there is no cytoplasmic accumulation of HOXA9 in Smad4(-/-) HSPCs and as a con

A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.

Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'- regulatory regions of candida