A5062422387- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Proteoglycans and glycosaminoglycans research
- Renal cell carcinoma treatment
- Mitochondrial Function and Pathology
- Congenital heart defects research
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Fibroblast Growth Factor Research
- Glioma Diagnosis and Treatment
- Renal and related cancers
- Autophagy in Disease and Therapy
- Gastric Cancer Management and Outcomes
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- TGF-β signaling in diseases
- Wound Healing and Treatments
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Radiomics and Machine Learning in Medical Imaging
- Monoclonal and Polyclonal Antibodies Research
- Phagocytosis and Immune Regulation
Turku University Hospital
2012-2024
University of Turku
2014-2024
Åbo Akademi University
2004-2021
Turku Centre for Computer Science
2021
University of Helsinki
2003-2020
Helsinki University Hospital
2019-2020
Turku Centre for Biotechnology
2006-2019
Centre for Human Genetics
2000-2001
University of Oxford
2000-2001
University of Oslo
2000
Hypoxia-inducible factor (HIF) is a transcriptional complex that plays central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-α subunits are rapidly destroyed mechanism involves ubiquitylation von Hippel–Lindau tumor suppressor (pVHL) E3 ligase complex. This process suppressed hypoxia chelation, allowing activation. Here we show interaction between human pVHL specific domain HIF-1α subunit regulated through hydroxylation proline residue (HIF-1α...
The von Hippel-Lindau tumor suppressor protein (pVHL) has emerged as a key factor in cellular responses to oxygen availability, being required for the oxygen-dependent proteolysis of α subunits hypoxia inducible factor-1 (HIF). Mutations VHL cause hereditary cancer syndrome associated with dysregulated angiogenesis, and up-regulation genes. Here we investigate mechanisms underlying these processes show that extracts from VHL-deficient renal carcinoma cells have defect HIF-α ubiquitylation...
<h3>Importance</h3> Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients operable gastrointestinal stromal tumor (GIST), but its influence on overall (OS) has remained uncertain. <h3>Objective</h3> To evaluate the effect of adjuvant OS who have a high estimated risk for GIST recurrence macroscopically complete surgery. <h3>Design, Setting, and Participants</h3> In this open-label, randomized (1:1), multicenter phase 3...
An important regulator involved in oxygen-dependent gene expression is the transcription factor HIF (hypoxia-inducible factor), which composed of an oxygen-sensitive α-subunit (HIF-1α or HIF-2α) and a constitutively expressed β-subunit. In normoxia, HIF-1α destabilized by post-translational hydroxylation Pro-564 Pro-402 family dioxygenases. The three HIF-modifying human enzymes have been termed prolyl hydroxylase domain containing proteins (PHD1, PHD2 PHD3). Prolyl leads to pVHL...
The structure of human syndecan, an integral membrane proteoglycan, has been determined by cloning its full-length cDNA, which codes for the entire 310-amino acid-long core protein, including NH2-terminal signal peptide. Similar to mouse syndecan (Saunders, S., Jalkanen, M., O'Farrell, and Bernfield, M. (1989) J. Cell Biol. 108, 1547-1556), protein can be divided into three domains: a matrix-interacting ectodomain containing putative glycosaminoglycan attachment sites, 25-residue hydrophobic...
The aim of the study is to assess value carbonic anhydrase isozyme IX (CA IX) expression as a predictor disease-free survival (DFS) and disease-specific (DSS) in rectal cancer treated by preoperative radio- or chemoradiotherapy surgery only. Archival tumour samples from 166 patients were analysed for CA three different evaluations: positive/negative, proportion positivity staining intensity. results immunohistochemical analysis confirmed demonstrating protein western blotting analysis....
Recent comprehensive assessments of RNA-seq technology support its utility in quantifying gene expression various samples. The next step rigorously differences between sample groups, however, still lacks well-defined best practices. Although a number advanced statistical methods have been developed, several studies demonstrate that their performance depends strongly on the data under analysis, which compromises practical real biomedical studies. As solution, we propose to use data-adaptive...
Abstract PURPOSE: Hypoxia in tumors is associated with poor prognosis and resistance to treatment. The outcome of hypoxia largely regulated by the hypoxia-inducible factors (HIF-1alpha HIF-2alpha). HIFs turn are negatively a family prolyl hydroxylases (PHD1-3). PHD2 isoform main down-regulator normoxia mild hypoxia. This study was designed analyze correlation expression subcellular localization pathologic features human carcinomas HIF-1alpha expression. EXPERIMENTAL DESIGN: studied from...
Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell-targeting therapies. Thus, agents able to reprogram macrophages toward a proinflammatory state hold promise as novel immunotherapies for solid cancers. Inhibition macrophage scavenger receptor Clever-1 has shown benefit inducing CD8
Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety tolerability blockade with bexmarilimab in patients treatment-refractory solid tumors assesses preliminary efficacy, pharmacodynamics, immunologic correlates. Bexmarilimab shows no dose-limiting toxicities part I (n = 30) additional signals II 108). Disease control (DC) rates 25%-40% are observed cutaneous melanoma, gastric,...
Low oxygen tension (hypoxia) contributes critically to pluripotency of human embryonic stem cells (hESCs) by preventing spontaneous differentiation and supporting self-renewal. However, it is not well understood how hESCs respond reduced availability what are the molecular mechanisms maintaining in these conditions. In this study we characterized transcriptional responses three hESC lines (H9, HS401 HS360) on short (2 hours), intermediate (24 hours) prolonged (7 days) exposure low conditions...
The HIF prolyl hydroxylases (PHDs/EGLNs) are central regulators of the molecular responses to oxygen availability. One isoform, PHD3, is expressed in response hypoxia and causes apoptosis oxygenated conditions neural cells. Here we show that PHD3 forms subcellular aggregates an oxygen-dependent manner. aggregation was seen under normoxia strongly reduced or by inactivation hydroxylase activity. were dependent on microtubular integrity contained components 26S proteasome, chaperones,...
Hypoxia restricts cell proliferation and cycle progression at the G1/S interface but least a subpopulation of carcinoma cells can escape restriction. In hypoxia may in fact select for with enhanced hypoxic survival increased aggressiveness. The cellular oxygen sensors HIF proline hydroxylases (PHDs) adapt functions to lowered environmental tension. PHD3 isoform has shown strongest upregulation among family members. We detected strong mRNA expression tumors head neck squamous (HNSCC)....
The receptor-tyrosine kinase ErbB4 was identified as a direct regulator of hypoxia-inducible factor-1α (HIF-1α) signaling. Cleaved intracellular domain directly interacted with HIF-1α in the nucleus, and stabilized protein both normoxic hypoxic conditions by blocking its proteasomal degradation. mechanism HIF stabilization independent VHL proline hydroxylation but dependent on RACK1. activity necessary for efficient HRE-driven promoter activity, transcription known target genes, survival...
Immune checkpoint inhibitors (ICI) have improved survival in several cancer types. Still, most patients develop disease progression during or after treatment. We evaluated the reasons for treatment discontinuation and their effect on outcomes adult with advanced ICI first later lines Southwest Finland between 1 January 2015 31 December 2021. Baseline characteristics were retrospectively obtained from electronic medical records. There 317 15 different types, commonly non-small cell lung...
Abstract Background Patients with ruptured gastrointestinal stromal tumour (GIST) have poor prognosis. Little information is available about how adjuvant imatinib influences survival. Methods We explored recurrence-free survival (RFS) and overall (OS) of patients GIST who participated in a randomised trial (SSG XVIII/AIO), where 400 high-risk were allocated to for either 1 year or 3 years after surgery. Of the 358 confirmed localised GIST, 73 (20%) had rupture reported. The ruptures...
Hypoxia is a common feature of advanced solid tumors causing cancer progression and resistance to treatment. activates mitophagy as well macroautophagy that regulates carcinoma cell survival. p62/SQSTM1, multifunctional protein targets proteins degradation by proteasomes autophagy, itself downregulated hypoxia-activated autophagy in cells. The hypoxic p62 seen across several lines. In contrast activation mitochondrial the hypoxia-induced occurs partially independently from HIF pathway....