Viola Heinzelmann‐Schwarz
A5057030543- Ovarian cancer diagnosis and treatment
- Glycosylation and Glycoproteins Research
- Endometrial and Cervical Cancer Treatments
- Cancer Cells and Metastasis
- PARP inhibition in cancer therapy
- Monoclonal and Polyclonal Antibodies Research
- BRCA gene mutations in cancer
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Intraperitoneal and Appendiceal Malignancies
- Uterine Myomas and Treatments
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Galectins and Cancer Biology
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Bone health and treatments
- Wnt/β-catenin signaling in development and cancer
- Oral and Maxillofacial Pathology
- Genetic factors in colorectal cancer
- Breast Cancer Treatment Studies
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Pelvic floor disorders treatments
- Cancer-related gene regulation
University Hospital of Basel
2016-2025
University of Basel
2016-2025
Olgahospital
2014-2024
Swiss Group For Clinical Cancer Research
2022-2023
Universitäts Frauenklinik
2016-2023
Peter MacCallum Cancer Centre
2012-2022
Hospital Base
2015-2022
National Cancer Centre Japan
2019-2022
UNSW Sydney
2011-2020
Royal Hospital for Women
2004-2020
The ability of circulating tumor cells (CTCs) to form clusters has been linked increased metastatic potential. Yet biological features and vulnerabilities CTC remain largely unknown. Here, we profile the DNA methylation landscape single CTCs from breast cancer patients mouse models on a genome-wide scale. We find that binding sites for stemness- proliferation-associated transcription factors are specifically hypomethylated in clusters, including OCT4, NANOG, SOX2, SIN3A, paralleling...
First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) pattern-recognition receptors binding a range of sialoglycan ligands, which appear function as self-associated molecular patterns (SAMPs) that suppress autoimmune...
Endogenous costimulatory molecules on T cells such as 4-1BB (CD137) can be leveraged for cancer immunotherapy. Systemic administration of agonistic anti-4-1BB antibodies, although effective preclinically, has not advanced to phase 3 trials because they have been hampered by both dependency Fcγ receptor-mediated hyperclustering and hepatotoxicity. To overcome these issues, we engineered proteins simultaneously targeting a tumor stroma or antigen: FAP-4-1BBL (RG7826) CD19-4-1BBL. In the...
Abstract Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients cancer, reflecting their contribution to the development tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates varying degrees organization and maturation. Specifically, mature TLSs (mTLS) as forming only 16% HGSOCs relatively elevated tumor mutational burden (TMB) are an increased...
Abstract The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety cancer types. In breast cancer, preclinical studies showed that inhibitors the Na + /K ATPase suppress CTC block metastasis. Here we conducted prospective, open-label, proof-of-concept study women metastatic where primary objective was to determine whether treatment inhibitor digoxin could reduce mean cluster size. An analysis nine patients treated daily...
Abstract Purpose: A better understanding of the molecular pathways underlying development epithelial ovarian cancer (EOC) is critical to identify tumor markers for use in diagnostic or therapeutic applications. The aims this study were integrate results from 14 transcript profiling studies EOC novel biomarkers and examine their expression early late stages disease. Experimental Design: database incorporating genes identified as being highly up-regulated each was constructed. Candidate...
Antibody-drug conjugates (ADC) are emerging as powerful treatment strategies with outstanding target-specificity and high therapeutic activity in patients cancer. Brentuximab vedotin represents a first-in-class ADC directed against CD30(+) malignancies. We hypothesized that its sustained clinical responses could be related to the stimulation of an anticancer immune response. In this study, we demonstrate dolastatin family microtubule inhibitors, from which cytotoxic component brentuximab is...
Selected reaction monitoring (SRM) is a targeted mass spectrometry technique that provides sensitive and accurate protein detection quantification in complex biological mixtures. Statistical computational tools are essential for the design analysis of SRM experiments, particularly studies with large sample throughput. Currently, most such focus on selection optimized transitions processing signals from assays. Little attention devoted to significance analysis, which combines quantitative...
Epithelial ovarian cancer is the fifth most common cause of in women worldwide bearing highest mortality rate among all gynecological cancers. Cell membrane glycans mediate various cellular processes such as cell signaling and become altered during carcinogenesis. The extent to which glycosylation changes are influenced by aberrant regulation gene expression nearly unknown for remains crucial understanding development progression this disease. To address effect, we analyzed non-cancerous...
The molecular repertoire promoting cancer cell plasticity is not fully elucidated. Here, we propose that glycosphingolipids (GSLs), specifically the globo and ganglio series, correlate promote transition between epithelial mesenchymal cells. character of ovarian remains stable throughout disease progression, spatial glycosphingolipidomics reveals elevated globosides in tumor compartment compared with ganglioside-rich stroma. CRISPR-Cas9 knockin mediated truncation endogenous E-cadherin...
Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of cancer. To determine genetic basis MOC to identify potential tumour markers, gene expression profiling 49 primary different was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that express profile both differs overlaps with Concordant its phenotype, genes characteristic mucinous carcinomas varying origin,...
Abstract High-grade serous cancer (HGSC), the most common subtype of ovarian cancer, often becomes resistant to chemotherapy, leading poor patient outcomes. Intratumoral heterogeneity occurs in nearly all solid cancers, including contributing development resistance mechanisms. In this study, we examined spatial and temporal genomic variation HGSC using high-resolution single-nucleotide polymorphism arrays. Multiple metastatic lesions from individual patients were analyzed along with 22...
Aberrant Wnt signalling is implicated in numerous human cancers, and understanding the effects of modulation pathway members may lead to development novel therapeutics. Expression secreted frizzled related protein 4 (SFRP4), an extracellular modulator pathway, progressively lost more aggressive ovarian cancer phenotypes. Here we show that recombinant SFRP4 (rSFRP4) treatment a serous cell line results inhibition β-catenin dependent as measured by TOP/FOP reporter assay decreased...
In recent years, the Wnt signalling pathway has been implicated in epithelial ovarian cancer and its members have potential as diagnostic, prognostic therapeutic targets. Here we investigated role of two receptor tyrosine kinases (RTKs), ROR1 ROR2, their putative ligand, Wnt5a, cancer.Immunohistochemistry for ROR2 was performed a large patient cohort, including benign controls, borderline tumours cancer. addition, siRNA used to silence ROR1, Wnt5a individually, together, cell lines, effects...
Recent technological advances have led to an increase in the production and availability of single-cell data. The ability integrate a set multi-technology measurements would allow identification biologically or clinically meaningful observations through unification perspectives afforded by each technology. In most cases, however, profiling technologies consume used cells thus pairwise correspondences between datasets are lost. Due sheer size can acquire, scalable algorithms that able...
The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset peritoneal cavity remains unexplored. Here, we suggest a new route metastasis through interaction integrin alpha 2 (ITGA2) with collagens enriched coinciding poor outcome patients ovarian cancer. Using multiple gene-edited cell lines patient-derived samples, demonstrate that ITGA2 triggers cancer adhesion collagen, promotes migration,...