A5016981900- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Breast Cancer Treatment Studies
- Molecular Biology Techniques and Applications
- Cancer Immunotherapy and Biomarkers
- Cancer Diagnosis and Treatment
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Cancer Treatment and Pharmacology
- Metastasis and carcinoma case studies
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Ferroptosis and cancer prognosis
- Cancer-related Molecular Pathways
- Metabolism, Diabetes, and Cancer
- RNA Research and Splicing
- Carcinogens and Genotoxicity Assessment
- Cancer-related molecular mechanisms research
- Systemic Lupus Erythematosus Research
- Breast Lesions and Carcinomas
- Medical Imaging Techniques and Applications
- Peptidase Inhibition and Analysis
- Cancer, Lipids, and Metabolism
KU Leuven
2023-2024
University of Sharjah
2021-2024
Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay the primary tumour or small biopsy. We assessed intra-patient inter-metastasis heterogeneity of status HER2-negative mBC.We included samples 10 patients (7 ER-positive and 3 ER-negative) donated context our post-mortem tissue donation program UPTIDER. Excisional biopsies 257 metastases 8 tumours underwent central HER2...
Abstract Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median 31 (range: 5-90) metastases 5-8 liquids per patient from its first 20 patients. In dedicated experiment, mild impact increasing time after death RNA quality, transcriptional profiles immunohistochemical staining in tumor samples. We that this can be counteracted organ cooling. successfully...
Primary tumors with a mixed invasive breast carcinoma of no-special type (IBC-NST) and lobular cancer (ILC) histology are present in approximately five percent all patients understudied at the metastatic level. Here, we characterized metastases from two primary IBC-NST/ILC postmortem tissue donation program UPTIDER (NCT04531696). The 14 43 lesions collected autopsy had morphological features E-cadherin staining patterns consistent pure ILC. While our findings still require further...
Aim: Colorectal cancer (CRC) is one of the leading cancers in world. Even though its mortality and pathophysiology are well documented US European countries, it seldom studied North African population. Recent studies have shown link HER2 overexpression oesophageal gastric cancers. The aim this study to assess protein mRNA expression correlation with tumor pathogenesis Libyan CRC patients.Methodology: A total 17 FFPE tissue blocks were collected from patients primary CRC. was assessed by...
Abstract Background. Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with HER2-low metastatic breast cancer. As the HER2-status can vary between primary and its corresponding metastases, treatment decisions should ideally be based on HER2 assessment of a recent biopsy. However, limited data is available intra-patient inter-metastatic heterogeneity HER2-status, affecting representability single biopsy potential therapeutic options outcome. We therefore assessed status...
Diabetes mellitus is a burdensome disease that affects various cellular functions through altered glucose metabolism. Several reports have linked diabetes to cancer development; however, the exact molecular mechanism of how diabetes-related traits contribute progression not fully understood. The current study aimed explore underlying potential effect hyperglycemia combined with hyperinsulinemia on breast cells. To this end, gene dysregulation induced by exposure MCF7 cells (HG), or...
Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the tissue. Whilst there a few studies that suggest an association between cancer, to best of our knowledge, this is first study identify common genes involved in severe cancer. Publicly available transcriptomic data for 23 epithelial brushings from asthmatics 55 samples formalin-fixed paraffin-embedded (FFPE) tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA)...
Primary tumors with a mixed no-special type (NST) and invasive lobular cancer (ILC) histology are present in approximately five percent of all patients breast understudied at the metastatic level. Here, we characterized metastases from two primary NST-ILC postmortem tissue donation program UPTIDER (NCT04531696). The 14 43 lesions collected autopsy had morphological features E-cadherin staining patterns consistent pure ILC. While our findings still require further clinical validation, they...
Abstract Background. Liquid biopsies represent a less invasive alternative to tissue biopsy characterize the disease in patients with metastatic cancer. Blood remains most frequently investigated body liquid regards detection, quantification and characterization of circulating tumor DNA (ctDNA). However, it might not capture full profile, other sources liquids may be complementary. The aim present study is compare ctDNA detection different types liquids. Patients methods. Sixteen from...
Abstract Background: Invasive lobular carcinoma (ILC) accounts for 15% of all invasive breast cancers (BC) and has a peculiar metastatic spread in comparison to BC no-special type. Since ILC is less likely disrupt normal tissue architecture usually non-mass forming, imaging lesions entails many challenges. Insights into pathologic versus radiological invasion can lead better diagnostic monitoring tools patients with ILC. Here, we compare microscopical findings during autopsy clinical prior...
Three Antibody-Drug Conjugates (ADCs), targeting HER2 or TROP2, are approved for metastatic breast cancer (mBC). ADCs another 55 targets currently being clinically studied in solid tumors. Here, we investigated the expression levels of all 57 targets, their correlation with tumor cellularity, inter- and intra-patient heterogeneity, co-expression, organ-specificity primary (P) samples (M) from patients enrolled our rapid autopsy program UPTIDER (NCT04531696). 650 (602 M, 48 P) 20 underwent...
Whole transcriptome analysis (WTA) using RNA extracted from Formalin Fixed Paraffin Embedded (FFPE) tissue is an invaluable tool to understand the molecular pathology of disease. FFPE either degraded and/or in very low quantities hampering gene expression analysis. Earlier studies described protocols applied for cellular poly-A primer-based linear amplification. The current study describes a method, LINCATRA (LINear amplifiCAtion whole TRAnscriptome analysis). It employs random nonamer...
Abstract Background: Obesity is a risk factor for postmenopausal hormone receptor-positive (HR+) breast cancer (BC) and associated with poorer outcomes. “Obesity-paradox”, phenomenon where obesity (BMI ≥ 30) better outcomes in patients treated immune checkpoint inhibitors (ICI), has been observed several types. It however under-explored BC, especially HR+ BC. Emerging data from recent trials (KEYNOTE-756 CheckMate 7FL) have shown the potential benefits of ICI treating early This prompted...
Abstract Background: Tumor progression still needs to be further elucidated in hormone receptor positive (HR+) breast cancer, the most common subtype of cancer. Here, leveraging extensive sampling approach our postmortem rapid tissue donation program UPTIDER (NCT04531696), we used phylogenic reconstruction analyze disease progression. Patients and Methods: Thirteen patients with HR+/HER2 non-amplified primary recruited between 12/2020 05/2022, were considered. Shallow whole-genome sequencing...
Abstract Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection (BCLM) is associated prolonged survival. However, there currently no validated marker to identify these patients. The interactions between the metastatic cells microenvironment result two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact hepatocytes, desmoplastic...
IC markers against which inhibitors are currently used/evaluated clinically, have not yet been studied in detail metastases (M) from patients with primary HR+/HER2- BC. In this study, we examined expression levels of these multiple M and tumors (P) BC who enrolled our postmortem tissue donation program UPTIDER (NCT04531696). 326 samples (23 untreated P 290 samples) 10 underwent bulk RNA sequencing (Lexogen). Quality control (QC) was set for 500000 assigned reads gene counts were normalized...
Glomerulonephritis (GN) is a complex disease with intricate underlying pathogenic mechanisms. The possible role of complement dysregulation not fully elucidated in some GN subsets, especially the setting autoimmunity or infection. In current study, diagnosed cases lupus nephritis (LN) and post-infectious (PIGN) were recruited for molecular genetic analysis targeted next-generation DNA sequencing was performed two main regulating genes: fluid phase; CFH , on tissue surfaces; MCP . Three...
Abstract Background. Research in metastatic breast cancer is hampered by limited sample availability. Post-mortem tissue donation programs can help to overcome this problem but are logistically challenging and have thus far mainly focused on histopathological genomic research. We here present the UPTIDER program (NCT04531696), aimed at multilevel characterization of advanced generation tumour models. Patients Methods. with stage IV receiving their last line(s) treatment eligible for...
Abstract Background. Postmortem tissue donation programs can importantly enhance sample access for translational research on metastatic disease. However, this post-mortem setting poses logistical and technical challenges in terms of preserving nucleic acid quality particular RNA. Here we present the results an experiment within our breast cancer program UPTIDER (NCT04531696), aiming at assessing RNA degradation rates expression profile changes function type sample-specific postmortem...
Abstract Background. Liquid biopsies represent a less invasive alternative to tissue biopsy characterize and possibly monitor the disease in patients with metastatic breast cancer. So far, blood remains most frequently investigated body liquid this context investigations mainly focus on detection, quantification characterization of circulating tumor DNA (ctDNA). However, since might not capture full profile, other sources liquids may have potential complement information obtained from blood....
HR+/HER2- BC is less immunogenic compared to triple-negative in the early setting. Lower levels of stromal tumor infiltrating lymphocytes (sTIL) are observed metastases primary tumor. sTIL have not yet been investigated extensively metastatic BC. Here, we aimed at evaluating multiple lesions from patients with who participated our institutional post-mortem tissue donation program UPTIDER (NCT04531696). 16 HR+ (ER+ and/or PR+)/HER2- BC, enrolled between 01/01/2021 and 08/01/2023 were...
Abstract Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection (BCLM) could be associated prolonged survival. However, there currently no validated marker to identify these patients. The interactions between the metastatic cells microenvironment result two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact hepatocytes,...