- Prostate Cancer Treatment and Research
- MicroRNA in disease regulation
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- RNA Research and Splicing
- Cancer, Lipids, and Metabolism
- Hormonal and reproductive studies
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Mesenchymal stem cell research
- Blood disorders and treatments
- Mass Spectrometry Techniques and Applications
- Steroid Chemistry and Biochemistry
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Prostate Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Estrogen and related hormone effects
- Cancer therapeutics and mechanisms
- Chronic Myeloid Leukemia Treatments
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Genomic variations and chromosomal abnormalities
University of Bern
2024
Meertens Institute
2003-2023
Princess Margaret Cancer Centre
2012-2022
Hospital for Sick Children
2015-2022
University Health Network
2011-2022
Radboud University Medical Center
2018
Radboud University Nijmegen
2018
University of Toronto
2010-2016
Erasmus MC
2003-2014
Ontario Institute for Cancer Research
2012-2013
To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated signature derived from functionally validated subpopulations of AML samples. For one miRNA, miR-126, high bioactivity aggregated all vivo patient sample LSC activity into single sorted population, tightly coupling miR-126 expression to function. Through functional studies, was found restrain cell cycle progression, prevent differentiation, and increase self-renewal...
Recently, a unique fusion between the prostate-specific, androgen-regulated TMPRSS2 gene and ETS genes ERG, ETV1, or ETV4 has been described in clinical prostate cancer. We investigated mechanisms of expression four genes, ETV4, FLI1, 11 xenografts representing different stages All five androgen-dependent showed as major transcript overexpression two splice variants TMPRSS2:ERG, linking exon 1 2 sequences to ERG 4. In one androgen-sensitive xenografts, transcripts ETV1 were detected....
SummaryThere is increasing evidence that some cancers are hierarchically organized, sustained by a relatively rare population of cancer-initiating cells (C-ICs). Although the capacity to initiate tumors upon serial transplantation hallmark all C-ICs, little known about genes control this process. Here, we establish ID1 and ID3 function together govern colon cell (CC-IC) self-renewal through cell-cycle restriction driven inhibitor p21. Regulation p21 central mechanism preventing accumulation...
Abstract Recently, fusion of ERG to the androgen-regulated, prostate-specific TMPRSS2 gene has been identified as most frequent genetic alteration in prostate cancer. At low frequency, TMPRSS2-ETV1 and TMPRSS2-ETV4 genes have described. In this study, we report two novel ETV4 cancer: KLK2-ETV4 CANT1-ETV4. Both fusions important unique aspects. KLK2 is a well-established androgen-induced gene. Fusion results generation an additional exon, denoted exon 4a. This delivers ATG for longest open...
In this study, we describe the properties of novel ETV1 fusion genes, encoding N-truncated (dETV1), and full-length ETV1, overexpressed in clinical prostate cancer. We detected overexpression genes or 10% cancers. Novel partners included FOXP1, an EST (EST14), endogenous retroviral repeat sequence (HERVK17). Like TMPRSS2, EST14 HERVK17 were prostate-specific androgen-regulated expressed. This unique expression pattern most seems important determinant cancer development. transient reporter...
To gain insight in the mechanism and clinical relevance of TMPRSS2-ERG expression prostate cancer, we determined specific characteristics fusion transcripts starting at TMPRSS2 exon 1 a more upstream less characterized 0.We used quantitative PCR analysis to investigate wild-type TMPRSS2(exon 0) 1) ERG transcripts. Expression was tested normal tissue samples, cancer cell lines xenografts, fresh-frozen samples (primary tumors recurrences). correlated with disease progression.TMPRSS2(exon were...
Peer support is an important unmet need among adolescent and young adult (AYA) cancer patients. This study was conducted to describe the use evaluation of a Dutch secure online community for AYA diagnosed with between 18 35 years.User statistics were collected Google analytics. Community members asked complete questionnaires on usefulness community. A content analysis using Linguistic Inquiry Word Count conducted.Between 2010 2017, received 433 (71% female; mean age at diagnosis 25.7 years;...
Abstract To study the mechanisms whereby androgen‐dependent tumors relapse in patients undergoing androgen blockade, we developed a novel progression model for prostate cancer. The PC346C cell line, established from transurethral resection of primary tumor, expresses wild‐type (wt) receptor (AR) and secretes prostate‐specific antigen (PSA). Optimal proliferation requires androgens is inhibited by antiandrogen hydroxyflutamide. Orthotopic injection dorsal‐lateral castrated athymic nude mice...
Abstract We examined 11 prostate cancer xenografts and 4 cell lines for chromosome 10 alterations. Conventional comparative genomic hybridization (CGH) array‐based CGH revealed a pattern of loss distal 10p, gain proximal 10p 10q, 10q. In addition, array identified 2 high‐level amplifications in the line PC3, homozygous deletions PTEN PC3 PCEW, PC133, PC324, small single‐ or double‐copy around PC82, PC346, LNCaP. Allelotype analysis confirmed all losses, 5 6 large 10q deletions, regions one...
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy, but the large number of HSCs required limits its widespread use. Host conditioning and donor composition are known to affect HSCT outcomes. However, specific role that posttransplantation signaling environment plays in HSC fate poorly understood. To mimic clinical HSCT, we injected human umbilical cord blood (UCB) cells at different doses compositions into immunodeficient NOD/SCID/IL-2Rgc-null (NSG) mice....
Abstract CD123 (IL-3Rα) is frequently expressed by malignant Hodgkin lymphoma (HL) cells. Naked monoclonal antibodies (mAb) against HL lack clinical benefit, partially due to absence of natural killer (NK) cells in the tumor microenvironment. Here we show that combination a fully humanized anti-CD123 mAb (CSL362) and high-affinity Fcγ-receptor NK-92 (haNK) effectively target kill vitro. First, confirmed high expression 2 3 cell lines (KM-H2 L-428), its NK Cytotoxicity haNK CD123-positive was...
Abstract A detailed analysis of chromosome 6 in DNAs from prostate cancers was performed, to define a region for subsequent search cancer genes. DNA 4 cell lines and 11 xenografts used CGH whole‐chromosome allelotyping with polymorphic microsatellite markers. Loss proximal 6q studied more detail by high‐density xenografts, 19 tumour specimens TURP. Seven 15 showed deletion CGH. Gain found 2 samples. Six samples 6p gain, 1 had loss. Allelotyping results were consistent data DNAs. In LNCaP...
Gene expression profiling and proteome analysis of normal malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this critical nexus. Here, we identify miR-130a as a regulator HSC self-renewal differentiation. Enforced impairs B lymphoid differentiation expands long-term HSCs. Integration mass spectrometry...
You have accessJournal of Urology1 Apr 2009OVEREXPRESSION OF PROSTATE-SPECIFIC TMPRSS2(EXON 0)-ERG FUSION TRANSCRIPTS CORRESPONDS WITH FAVORABLE PROGNOSIS PROSTATE CANCER Joost Boormans, Karin G Hermans, Geert J van Leenders, Paul C Verhagen, and Jan Trapman BoormansJoost Boormans More articles by this author , HermansKarin Hermans LeendersGeert Leenders VerhagenPaul Verhagen TrapmanJan View All Author Informationhttps://doi.org/10.1016/S0022-5347(09)60743-6AboutPDF ToolsAdd to...
BACKGROUND: Cerebral intraventricular hemorrhage (IVH) is a major cause of neurodevelopmental impairment in preterm infants.IVH characterized by vessel rupture and rapid accumulation blood within the ventricles.Subsequent hemolysis leads to release extracellular hemoglobin (Hb) into cerebrospinal fl uid (CSF).Hb its metabolites initiate cytotoxic, oxidative, proinfl ammatory, apoptotic pathways resulting tissue damage.Scavenging Hb, using haptoglobin (Hp), may therefore constitute potential...