A5063778910- PARP inhibition in cancer therapy
- Peptidase Inhibition and Analysis
- Prostate Cancer Treatment and Research
- Lung Cancer Research Studies
- Statistical Methods in Clinical Trials
- Bladder and Urothelial Cancer Treatments
- Metal complexes synthesis and properties
- Prostate Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Lipoproteins and Cardiovascular Health
- Ferroptosis and cancer prognosis
- Cancer Research and Treatments
- Mathematical Biology Tumor Growth
- Cancer, Hypoxia, and Metabolism
- Hormonal and reproductive studies
- Endometriosis Research and Treatment
- Optimal Experimental Design Methods
- Estrogen and related hormone effects
- Ferrocene Chemistry and Applications
- Cancer Genomics and Diagnostics
- Atherosclerosis and Cardiovascular Diseases
- Advanced Proteomics Techniques and Applications
- Endometrial and Cervical Cancer Treatments
University of Colorado Anschutz Medical Campus
2017-2024
University of Turku
2015-2024
University of Helsinki
2012-2024
Helsinki University Hospital
2024
Discovery Institute
2023
University of Pittsburgh
2023
Institute for Molecular Medicine Finland
2011-2022
University of Colorado Denver
2020-2022
Turku University Hospital
2022
Turku Centre for Computer Science
2021
Low-density lipoprotein (LDL) particles cause atherosclerotic cardiovascular disease (ASCVD) through their retention, modification, and accumulation within the arterial intima. High plasma concentrations of LDL drive this disease, but quality may also contribute. Here, we focused on intrinsic propensity to aggregate upon modification. We examined whether inter-individual differences in are linked with lipid composition coronary artery (CAD) death, basic mechanisms for plaque growth...
The insult leading to autoantibody development in children who will progress develop type 1 diabetes (T1D) has remained elusive. To investigate the genes and molecular pathways pathogenesis of this disease, we performed genome-wide transcriptomics analysis on a unique series prospective whole-blood RNA samples from at-risk collected Finnish Type Diabetes Prediction Prevention study. We studied 28 autoantibody-positive children, out which 22 progressed clinical disease. Collectively, covered...
Pharmacological PP2A activation is a druggable approach to overcome MEK inhibitor resistance.
The recommended treatment for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) instillations. However, only 50% of benefit from this therapy. If progression to advanced disease occurs, then must undergo a radical cystectomy risks substantial morbidity and poor clinical outcome. Identifying tumors unlikely respond BCG can translate into alternative treatments, such as early cystectomy, targeted...
Abstract Background Chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) is increasingly being applied to study transcriptional regulation on a genome-wide scale. While numerous algorithms have recently been proposed for analysing the large ChIP-seq datasets, their relative merits and potential limitations remain unclear in practical applications. Results The present compares state-of-the-art detecting transcription factor binding sites four diverse datasets...
Abstract Elevated MYC expression sensitizes tumor cells to apoptosis but the therapeutic potential of this mechanism remains unclear. We find, in a model MYC-driven breast cancer, that pharmacological activation AMPK strongly synergizes with BCL-2/BCL-X L inhibitors activate apoptosis. demonstrate translational an and co-targeting strategy ex vivo models MYC-high cancer. Metformin combined navitoclax or venetoclax efficiently inhibited growth, conferred survival benefits induced infiltration...
Protein phosphatase 2A (PP2A) critically regulates cell signaling and is a human tumor suppressor. PP2A complexes are modulated by proteins such as cancerous inhibitor of protein (CIP2A), methylesterase 1 (PME-1), SET nuclear proto-oncogene (SET) that often deregulated in cancers. However, how they impact cellular phosphorylation redundant regulation poorly understood. Here, we conducted systematic phosphoproteomics screen for phosphotargets siRNA-mediated depletion CIP2A, PME-1, (to...
Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from Anti-PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled assessment predictive models by using data two randomized controlled clinical trials (RCTs) ICIs in first-line metastatic NSCLC.
Aberrant sex steroid signaling is suggested to promote endometriosis growth by several mechanisms, and the tissue concentrations of steroids are key determinants hormone action. However, their only superficially known in endometrium lesions.This study sought evaluate whether differ from or serum.Steroid analysis serum specimens women with (n = 60) healthy controls (n=16) was measured, supporting data quantitative RT-PCR for steroidogenic enzymes explant cultures a subset provided.Endometrial...
The hydroxysteroid (17beta) dehydrogenase (HSD17B)12 gene belongs to the (17β) superfamily, and it has been implicated in conversion of estrone estradiol as well synthesis arachidonic acid (AA). AA is a precursor prostaglandins, which are involved regulation female reproduction, prompting us study role HSD17B12 enzyme ovarian function. We found broad expression both human mouse ovaries. was localized theca interna, corpus luteum, granulosa cells, oocytes, surface epithelium. Interestingly,...
Hyperactivated RAS drives progression of many human malignancies. However, oncogenic activity is dependent on simultaneous inactivation protein phosphatase 2A (PP2A) activity. Although PP2A known to regulate some the effector pathways, it has not been systematically assessed how these proteins functionally interact. Here we have analyzed phosphoproteomes regulated by either or PP2A, phosphopeptide enrichment followed mass-spectrometry-based label-free quantification. To allow data...
Abstract Endometriosis is a common inflammatory estrogen-dependent gynecological disorder, associated with pelvic pain and reduced fertility in women. Several aspects of this disorder its cellular molecular etiology remain unresolved. We have analyzed the global gene expression patterns endometrium, peritoneum endometriosis lesions patients endometrium healthy In report, we present EndometDB, an interactive web-based user interface for browsing database collected samples without need...
Importance Magnetic Resonance Imaging (MRI) coupled with Prostate Imaging-Reporting and Data System (PI-RADS) provides a standardized scoring system for assessing clinical significance of prostate cancer (PCa). However, the association between PI-RADS scores key end-points remains underexplored due to limited follow-up data. Objective To evaluate cancer-specific mortality (PCSM), overall survival (OS), metastasis-free (MFS), biochemical recurrence (BCR) across multiple cohorts. Design,...
Abstract Recent reports have called into question the reproducibility, validity and translatability of preclinical animal studies due to limitations in their experimental design statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization power calculations, which takes full account complex characteristics at baseline prior interventions. In prostate cancer xenograft studies, method effectively normalized...
There is an unmet need to improve the efficacy of platinum-based cancer chemotherapy, which used in primary and metastatic settings many types. In bladder cancer, chemotherapy leads better outcomes a subset patients when neoadjuvant setting or combination with immunotherapy for advanced disease. Despite such promising results, extending benefits platinum drugs greater number highly desirable. Using multiomic assessment cisplatin-responsive -resistant human cell lines whole-genome CRISPR...
Abstract Purpose: Preclinical tumor growth experiments often result in heterogeneous datasets that include growing, regressing, or stable profiles the treatment and control groups. Such confounding intertumor variability may mask true effects especially when less aggressive alternatives are being evaluated. Experimental design: We developed a statistical modeling approach which growing poorly categories were automatically detected by means of an expectation-maximization algorithm coupled...
Prostate cancer is the most common of men in Western world, and novel approaches for prostate risk reduction are needed. Plant-derived phenolic compounds attenuate growth preclinical models by several mechanisms, which line with epidemiological findings suggesting that consumption plant-based diets associated low cancer. The objective this study was to assess effects a lignan-stilbenoid mixture PC-3M-luc2 human cells vitro orthotopic xenografts. Lignan stilbenoid –rich extract obtained from...
What is the role of SFRP2 in endometriosis? acts as a canonical WNT/CTNNB1 signaling agonist endometriosis, regulating endometriosis lesion growth and indicating borders together with CTNNB1 (also known beta catenin). Endometriosis common, chronic disease that affects women reproductive age, causing pain infertility, has significant economic impact on national health systems. Despite extensive research, pathogenesis poorly understood, targeted medical treatments are lacking. WNT dysregulated...
Antibiotic treatment may reduce the efficacy of cancer immunotherapy by disrupting gut microbiome. We aimed to study association antibiotics and survival outcomes in advanced cutaneous melanoma non-small-cell lung (NSCLC) patients who had received anti-PD-1/L1 monotherapy.A total 222 199 NSCLC monotherapy 5 Finnish hospitals between January 2014 December 2020. Clinical characteristics, antibiotic corticosteroid treatment, were retrospectively collected from hospital national medical...
Abstract Background Hypoxia inducible factors, HIF‐1α and HIF‐2α, their main regulators, the prolyl hydroxylase domain proteins (PHDs), mediate cellular response to hypoxia contribute tumor progression in clear cell renal carcinoma (ccRCC). These biomarkers may improve value of traditional histopathological features predicting disease after nephrectomy for localized ccRCC guide patient selection adjuvant treatments. Patients Methods In this study, we analyzed associations PHD2 PHD3 with...