A5088378449- Ovarian cancer diagnosis and treatment
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Pediatric Hepatobiliary Diseases and Treatments
- FOXO transcription factor regulation
- Congenital Anomalies and Fetal Surgery
- Molecular Biology Techniques and Applications
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Pancreatic and Hepatic Oncology Research
- Gallbladder and Bile Duct Disorders
- Neuroendocrine Tumor Research Advances
- T-cell and B-cell Immunology
- Lung Cancer Research Studies
- Immunodeficiency and Autoimmune Disorders
- Sirtuins and Resveratrol in Medicine
- Reproductive Biology and Fertility
- Immune Cell Function and Interaction
- PI3K/AKT/mTOR signaling in cancer
- Long-Term Effects of COVID-19
- Ovarian function and disorders
- Genetic and phenotypic traits in livestock
- Endometrial and Cervical Cancer Treatments
- Cancer Mechanisms and Therapy
University of Helsinki
2014-2023
Helsinki University Hospital
2014-2023
University of Jyväskylä
2018
Vancouver General Hospital
2016
University of British Columbia
2016
McGill University Health Centre
2016
BC Cancer Agency
2016
Helsinki Children's Hospital
2014
Washington University in St. Louis
2014
During late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such development. Here, we use MULTI-seq generate scRNA-seq profiles over 66,000 cells from 36 mice normal or impaired secondary hyperoxia with validation some the findings lungs BPD...
Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy processes high-grade serous ovarian cancer, we prospectively collected tissue samples before after analyzed their transcriptomic profiles at single-cell resolution. After removing patient-specific signals by novel analysis approach, PRIMUS, found consistent increase stress-associated cell state during chemotherapy, which was validated RNA situ...
FOXL2 is a transcription factor that essential for ovarian function and maintenance, the germline mutations of which are responsible Blepharophimosis Ptosis Epicanthus-inversus Syndrome (BPES), often associated with premature failure. Recent evidence has linked downregulation or somatic mutation (p.Cys134Trp) to cancer, although underlying molecular mechanisms remain unclear. Using functional genomic approach, we find modulates cell-cycle regulators in way tends induce G1 arrest. Indeed,...
The histopathologic features of adult granulosa cell tumors (AGCTs) are relatively nonspecific, resulting in misdiagnosis other cancers as AGCT, a problem that has not been well characterized. FOXL2 mutation testing was used to stratify 336 AGCTs from three European centers into categories: 1) mutant molecularly defined AGCT (MD-AGCT) (n = 256 336), 2) wild-type 17 3) misdiagnosed tumor types 63 336). All statistical tests were two-sided. overall and disease-specific survival the cases lower...
A truncated variant of Helios causes a human immunodeficiency disease with signs immune overactivation.
Background and Aims: Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. Approach Results: Serum liver specimens, obtained from patients (N=87) at or age-matched cholestatic controls (N=26) were included. concentration FGF19 bile acids, mRNA expression , key regulators acid synthesis related to histopathology. Immunohistochemistry in...
Aberrant ovarian granulosa cell proliferation and apoptosis may lead to tumors (GCT), the pathogenesis of which involves transcription factors GATA4, FOXL2, SMAD3. FOXL2 gene harbors a point mutation (C134W) in vast majority GCTs. GATA4 is abundantly expressed GCTs its expression correlates with poor prognosis. The TGF-β mediator SMAD3 promotes GCT survival through NF-κB activation, interacts FOXL2. Here, we find that patterns these overlap normal human ovary 90 GCTs, positively correlate...
Circulating tumor DNA (ctDNA) detection is a minimally invasive technique that offers dynamic molecular snapshots of genomic alterations in cancer. Although ctDNA markers can be used for early cancers or monitoring treatment efficacy, the value guiding decisions solid controversial. Here, we monitored to detect clinically actionable during high-grade serous ovarian cancer, most common and aggressive form epithelial cancer with 5-year survival rate 43%.We implemented clinical workflow more...
Abstract Granulosa cell tumors (GCTs) carry a risk of recurrence also at an early stage, but reliable prognostic factors are lacking. We assessed clinicopathological and the roles human epidermal growth factor receptors (HER 2–4) transcription GATA4 in GCTs. conducted long‐term follow‐up study 80 GCT patients with mean time 16.8 years. A tumor‐tissue microarray was immunohistochemically stained for HER2–4 GATA4. Expression mRNA studied by means real polymerase chain reaction HER2 gene...
A major challenge in analyzing cancer patient transcriptomes is that the tumors are inherently heterogeneous and evolving. We analyzed 214 bulk RNA samples of a longitudinal, prospective ovarian cohort found sample composition changes systematically due to chemotherapy between anatomical sites, preventing direct comparison treatment-naive treated samples.To overcome this, we developed PRISM, latent statistical framework simultaneously extract cell-type-specific whole-transcriptome profiles...
RNA in situ hybridization (RNA-ISH) is a powerful spatial transcriptomics technology to characterize target abundance and localization individual cells. This allows analysis of tumor heterogeneity expression localization, which are not readily obtainable through transcriptomic data analysis. RNA-ISH experiments produce large amounts there need for automated methods. Here we present QuantISH, comprehensive open-source image pipeline that quantifies marker expressions carcinoma, immune,...
Platinum-resistance is a major limitation to effective chemotherapy regimens in high-grade serous ovarian cancer (HGSOC). To better understand the mechanisms involved we characterized proteome and phosphoproteome cisplatin sensitive resistant HGSOC primary cells using mass spectrometry-based proteomic strategy. PCA analysis identified distinctive phosphoproteomic signature between cell lines. The most phosphorylated protein was sequestosome-1 (p62/SQSTM1). Changes expression of apoptosis...
Abstract Adult-type granulosa cell tumors (AGCTs) are sex-cord derived neoplasms with a propensity for late relapse. Hormonal modulators have been used empirically in the treatment of recurrent AGCT, albeit limited success. To provide more rigorous foundation hormonal therapy we multimodal approach to characterize expressions key hormone biomarkers 175 tumor specimens and 51 serum samples using RNA sequencing, immunohistochemistry, situ hybridization, quantitative PCR, circulating biomarker...
Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated ductular reaction and liver fibrogenesis. We studied serum IL-8 expression large biliary atresia (BA) cohort explored its prognostic pathophysiological potential. was assessed utilizing quantitative polymerase chain (qPCR), immunohistochemistry situ hybridization using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls 68 normal controls. Results were correlated to...
Biliary atresia (BA), a neonatal liver disease, is characterized by obstruction of extrahepatic bile ducts with subsequent cholestasis, inflammation, and progressive fibrosis. To gain insights into the pathophysiology BA, we focused attention on GATA6, transcription factor implicated in biliary development. Early fetal development GATA6 expression evident cholangiocytes hepatocytes, but late gestation it extinguished hepatocytes. Utilizing unique set BA samples collected before after...
GATA4, a transcription factor crucial for early liver development, has been implicated in the pathophysiology of hepatoblastoma, an embryonal tumor childhood. However, molecular and phenotypic consequences GATA4 expression hepatoblastoma are not fully understood. We surveyed 24 hepatoblastomas using RNA situ hybridization immunohistochemistry. interference was used to inhibit human HUH6 cells, changes cell migration were measured with wound healing transwell assays. microarray performed on...
Background Sentinel node biopsy (SNB) is an important step in melanoma staging and prognostication. It commonly performed for patients with intermediate thickness melanomas, based on clinicopathological features. However, only 20–25% of eventually demonstrate nodal involvement. The aim this study was to evaluate whether tissue biomarkers links biology, together parameters, could aid the prediction sentinel involvement improve selection SNB. In addition, we examined role these clinical or...
Successful portoenterostomy (SPE) improves the short-term outcome of patients with biliary atresia (BA) by relieving cholestasis and extending survival native liver. Despite SPE, hepatic fibrosis progresses in most patients, leading to cirrhosis a deterioration liver function. The goal this study was characterize effects SPE on BA transcriptome. We used messenger RNA sequencing analyze global gene-expression patterns biopsies obtained at time (n = 13) 1 year after 8). Biopsies from pediatric...
Defects in the mRNA export scaffold protein GANP, encoded by MCM3AP gene, cause autosomal recessive early-onset peripheral neuropathy with or without intellectual disability. We extend here phenotypic range associated variants, describing a severely hypotonic child and sibling pair progressive encephalopathic syndrome. In addition, our analysis of skin fibroblasts from affected individuals seven unrelated families indicates that disease variants result depletion GANP except when they alter...
Abstract Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high to both adenocarcinomas neuroendocrine tumors yet be described. We studied family 16 individuals in four generations affected by wide spectrum tumors, including hyperplastic polyps, adenomas, colorectal To assess the genetic susceptibility understand novel phenotype, we utilized multiple molecular methods, whole genome sequencing,...
Epidermal growth factor receptor (EGFR) is implicated in the progression of many human cancers, but its significance ovarian granulosa cell tumor (GCT) pathobiology remains poorly understood. We assessed EGFR gene copy number, surveyed mRNA and protein expression patterns 90 adult GCTs, vitro sensitivity GCT cells to inhibition. Low-level amplification was observed five GCTs high-level one sample. robustly expressed GCTs. Most tumors both unphosphorylated phosphorylated protein, did not...