A5080745454- Cancer Immunotherapy and Biomarkers
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- PARP inhibition in cancer therapy
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- DNA Repair Mechanisms
- Ovarian cancer diagnosis and treatment
- Colorectal Cancer Treatments and Studies
- Cancer-related Molecular Pathways
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- COVID-19 and healthcare impacts
- Machine Learning in Bioinformatics
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Cytokine Signaling Pathways and Interactions
- Cervical Cancer and HPV Research
- Breast Cancer Treatment Studies
- MicroRNA in disease regulation
- Global Cancer Incidence and Screening
- Cancer, Stress, Anesthesia, and Immune Response
University Medical Center Groningen
2018-2025
University of Groningen
2018-2025
Westmead Hospital
2024
Bankura Sammilani Medical College
1993
Two monoclonal antibodies to mouse Ia antigens were produced by fusion of xenoimmune rat spleen cells with the NSI myeloma. These detect polymorphic determinants present on B and activated T lymphocytes from mice carrying H-2b, H-2d, H-2k, H-2r, H-2q haplotypes but not H-2s or H-2r haplotypes. Antigenic site number determinations showed positive can be divided into 2 groups. Mice bearing express a high number--40,000 80,000--of antigenic sites per lymphocyte, antibody plus complement lyse...
Abstract The limited efficacy of immune checkpoint inhibitor treatment in triple-negative breast cancer (TNBC) patients is attributed to sparse or unresponsive tumor-infiltrating lymphocytes, but the mechanisms that lead a therapy resistant tumor microenvironment are incompletely known. Here we show strong correlation between MYC expression and loss signatures human TNBC. In mouse models TNBC proficient deficient type 1 susceptibility gene (BRCA1), overexpression dramatically decreases...
Abstract Copy number alterations (CNAs) can promote tumor progression by altering gene expression levels. Due to transcriptional adaptive mechanisms, however, CNAs do not always translate proportionally into altered By reanalyzing >34,000 profiles, we reveal the degree of adaptation in a genome-wide fashion, which strongly associate with distinct biological processes. We then develop platform-independent method—transcriptional CNA profiling (TACNA profiling)—that extracts effects from...
Abstract Oncogene-induced replication stress, for instance as a result of Cyclin E1 overexpression, causes genomic instability and has been linked to tumorigenesis. To survive high levels tumors depend on pathways deal with these DNA lesions, which represent therapeutically actionable vulnerability. We aimed uncover the consequences or Cdc25A overexpression kinetics, mitotic progression, sensitivity inhibitors WEE1 ATR checkpoint kinases. modeled oncogene-induced stress using inducible...
Joint DNA molecules are natural byproducts of replication and repair. Persistent joint give rise to ultrafine bridges (UFBs) in mitosis, compromising sister chromatid separation. The translocase PICH (ERCC6L) has a central role UFB resolution. A genome-wide loss-of-function screen is performed identify the genetic context dependency. In addition genes involved condensation, centromere stability, DNA-damage repair, we FIGNL1-interacting regulator recombination mitosis (FIRRM), formerly known...
Abstract The interpretation of high throughput sequencing data is limited by our incomplete functional understanding coding and non-coding transcripts. Reliably predicting the function such transcripts can overcome this limitation. Here we report use a consensus independent component analysis guilt-by-association approach to predict over 23,000 groups comprised 55,000 using publicly available transcriptomic profiles. We show that, compared Principal Component Analysis, Independent...
Abstract Background The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to scraping by a general practitioner (GP), women are offered self-sampling increase participation. Because cytological examination on self-sampled material is not feasible, collection samples from hrHPV-positive GP required. This study aims design methylation marker panel detect CIN3 or worse...
Background Cyclin E1 overexpression drives oncogenesis in several cancers through deregulation of DNA replication and induction genomic instability, which may potentially trigger immune signaling via cytoplasmic DNA. However, the effects cyclin on tumor immunity its response to checkpoint inhibitors remain largely unclear. Methods Tissue microarrays clinical outcomes 398 patients with breast cancer were analyzed explore correlation between expression, patient survival, cell infiltration...
Bulk transcriptomic analyses of high-grade serous ovarian cancer (HGSOC) so far have not uncovered potential drug targets, possibly because subtle, disease-relevant transcriptional patterns are overshadowed by dominant, non-relevant ones. Our aim was to uncover disease-outcome-related in HGSOC transcriptomes that may reveal novel targets.Using consensus-independent component analysis, we dissected 678 systemic therapy naïve patients—sourced from public repositories—into statistically...
Amplification of the MYC proto-oncogene is frequently observed in various cancer types, including triple negative breast (TNBC). Emerging evidence suggests that suppression local anti-tumor immune responses by MYC, at least part, explains tumor-promoting effects MYC. Specifically, upregulation was demonstrated to suppress tumor-cell intrinsic activation a type I IFN response and thereby hamper innate inflammatory signaling, which may contribute disappointing immunotherapy patients with TNBC....
Bulk transcriptomic analyses of high-grade serous ovarian cancer (HGSOC) so far have not uncovered potential drug targets, possibly because subtle, disease-relevant transcriptional patterns are overshadowed by dominant, non-relevant ones. Our aim was to uncover disease-outcome-related in HGSOC transcriptomes that may reveal novel targets. Using consensus-independent component analysis, we dissected 678 systemic therapy naïve patients—sourced from public repositories—into statistically...
12048 Background: Testicular cancer (TC) survivors face an increased risk of cardiovascular diseases (CVD) as a late adverse effect oncological treatment, especially after cisplatin-based chemotherapy. To explore genetic susceptibility, we performed genome-wide association study using hierarchical clustering and assessed impact polygenic scores (PRS). Methods: A subcohort TC patients treated at expert centers in the Netherlands between 1976 2007 was established by hospital stratified random...
A xenogeneic rat anti-mouse Ia monoclonal antibody, M5/114 (gamma 2b, kappa), was studied for its effects in vitro on T cell proliferative responses. Strain distribution studies revealed that could inhibit I-A subregion-restricted responses of the H-2b,d,q,u but not H-2f,k,s haplotypes, indicating this xenoantibody recognizes a polymorphic determinant mouse molecules. This same antibody found to BALB/c (H-2d) proliferation both G60A30T10 and G58L38 phi 4. The Ir genes regulating these...
Numerous transcriptomic-based models have been developed to predict or understand the fundamental mechanisms driving biological phenotypes. However, few successfully transitioned into clinical practice due challenges associated with generalizability and interpretability. To address these issues, researchers turned dimensionality reduction methods begun implementing transfer learning approaches.
Abstract Immune checkpoint inhibitor (ICI) treatment has thus far shown limited efficacy in triple-negative breast cancer (TNBC) patients, presumably due to sparse or unresponsive tumor-infiltrating lymphocytes. We reveal a strong correlation between MYC expression and loss of immune signatures human TNBC. In mouse models BRCA1-proficient -deficient TNBC, overexpression dramatically decreased lymphocyte infiltration tumors, along with signature loss. Likewise, suppressed inflammatory...
Abstract Background Bulk transcriptional profiles of early colorectal cancer (CRC) can fail to detect biological processes associated with disease-free survival (DFS) if the patterns are subtle and/or obscured by other processes’ patterns. Consensus-independent component analysis (c-ICA) dissect such transcriptomes into statistically independent components (TCs), capturing both pronounced and processes. Methods In this study we (1) integrated ( n = 4228) from multiple CRC studies, (2)...
Abstract Replication stress (RS) is a key trait of cancer cells, and potential actionable target in treatment. Accurate methods to measure RS tumour samples are currently lacking. DNA fibre analysis has been used as common technique cell lines. Here, we investigated on fresh breast specimens correlated replication kinetics known markers genomic alterations. Fresh, treatment‐naïve primary ( n = 74) were subjected ex vivo kinetics. Tumour proliferation was confirmed by EdU incorporation...