Paul N. Span
A5090664851- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Sexual Differentiation and Disorders
- RNA modifications and cancer
- Hormonal and reproductive studies
- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- Head and Neck Cancer Studies
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cytokine Signaling Pathways and Interactions
- Mitochondrial Function and Pathology
- Cell Adhesion Molecules Research
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- Genomics and Chromatin Dynamics
- Autophagy in Disease and Therapy
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Radiomics and Machine Learning in Medical Imaging
- Breast Cancer Treatment Studies
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
Radboud University Nijmegen
2016-2025
Radboud University Medical Center
2016-2025
University Medical Center
2001-2024
Radboud Institute for Molecular Life Sciences
2017-2022
Prostate Cancer Research
2016
Erasmus MC Cancer Institute
2014-2016
University of Minnesota
2016
Radiation Oncology Associates
2014
University Medical Center Utrecht
2012-2014
Maastricht University Medical Centre
2012-2014
For interpretation of quantitative gene expression measurements in clinical tumor samples, a normalizer is necessary to correct data for differences cellular input, RNA quality, and RT efficiency between samples. In many studies, single housekeeping used normalization. However, no unequivocal reference (with proven invariable cells) has been identified yet. As the best alternative, mean multiple genes can be this study, attempt was made determine gold-standard normalization, but identify...
Introduction The human genome is peppered with mobile repetitive elements called long interspersed nuclear element–1 (L1) retrotransposons. Propagating through RNA and cDNA intermediates, these molecular parasites copy insert themselves throughout the genome, potentially disruptive effects on neighboring genes or regulatory sequences. In germ line, unique sequence downstream of L1 can also be retrotransposed if transcription continues beyond repeat, a process known as 3′ transduction. There...
We previously identified in a single-center study 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this was to validate gene an independent more diverse population LNN patients from multiple institutions.Using custom-designed DNA chips we analyzed the expression 76 genes RNA frozen tumor samples 180 who did not receive adjuvant systemic treatment.In validation, highly informative identifying with distant metastasis within 5 years (hazard ratio,...
Abstract Somatic mutations in human cancers show unevenness genomic distribution that correlate with aspects of genome structure and function. These are, however, generated by multiple mutational processes operating through the cellular lineage between fertilized egg cancer cell, each composed specific DNA damage repair components leaving its own characteristic signature on genome. Using somatic mutation catalogues from 560 breast whole-genome sequences, here we 12 base substitution, 2...
To report the results from a randomized trial comparing accelerated radiotherapy (AR) with plus carbogen inhalation and nicotinamide (ARCON) in laryngeal cancer.Patients cT2-4 squamous cell cancer were randomly assigned to AR (68 Gy within 36 38 days) or ARCON. limit risk of necrosis, ARCON patients received 64 on cartilage. The primary end point was local control. Secondary points regional control, larynx preservation, toxicity, disease-free survival, overall survival. In translational side...
Abstract Purpose: Tumor hypoxia is associated with a poor prognosis, modification improves outcome, and hypoxic status predicts benefit from treatment. Yet, there no universal measure of clinical hypoxia. The aim this study was to investigate whether 26-gene signature predicted hypoxia-modifying treatment in both cancer types. Experimental Design: Samples were available 157 T2–T4 laryngeal 185 T1–T4a bladder patients enrolled on the accelerated radiotherapy carbogen nicotinamide (ARCON)...
The hypoxia-inducible factor (HIF)-1 pathway can stimulate tumor cell migration and metastasis. Furthermore, hypoxic tumors are associated with a poor prognosis. Besides the HIF-1 pathway, unfolded protein response (UPR) is also induced by conditions. PKR-like ER kinase (PERK)/activating transcription 4 (ATF4)-arm of UPR induces expression lysosomal-associated membrane 3 (LAMP3), that has been linked to metastasis prognosis in solid tumors. In this study role UPR-induced LAMP3...
An antiviral enzyme promotes drug resistance in breast cancer.
TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. has been implicated in control of cell adhesion and migration, but whether activity contributes to cancer progression not established. Here we report that high levels expression independently predict poor outcome breast patients it is functionally required for metastasis formation mouse xenograft model human cancer. Mechanistic investigation revealed regulated myosin II-based cellular tension, thereby modifying...
Abstract Collagenase-2 (matrix metalloproteinase-8, MMP-8) is an MMP mainly produced by neutrophils and associated with many inflammatory conditions. We have previously described that MMP-8 plays a protective role in cancer through its ability to regulate the response induced carcinogens. Moreover, it has been reported experimental manipulation of expression levels this enzyme alters metastatic behavior human breast cells. In work, we used mutant mice deficient syngenic melanoma lung...
Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has been proposed as a potential therapeutic strategy; however, the transcriptional targets that mediate p53-dependent remain elusive. Here, we demonstrated is reliant on DNA-binding and transactivation domains but not acetylation sites K120 K164, which, contrast, are essential for DNA damage-induced, apoptosis. Evaluation transcripts multiple cell lines identified group genes hypoxia-inducible proapoptotic p53,...