A5068715101- Histone Deacetylase Inhibitors Research
- Testicular diseases and treatments
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Bladder and Urothelial Cancer Treatments
- Ovarian cancer diagnosis and treatment
- Sarcoma Diagnosis and Treatment
- Genomics, phytochemicals, and oxidative stress
- Autophagy in Disease and Therapy
- Cancer therapeutics and mechanisms
- Immunotherapy and Immune Responses
- Glutathione Transferases and Polymorphisms
- Urologic and reproductive health conditions
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Multiple Myeloma Research and Treatments
- Immune cells in cancer
- Tissue Engineering and Regenerative Medicine
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Cell death mechanisms and regulation
- Cervical Cancer and HPV Research
- Advanced Breast Cancer Therapies
- Immune Cell Function and Interaction
- Genital Health and Disease
Heinrich Heine University Düsseldorf
2016-2025
Düsseldorf University Hospital
2017-2025
Klinik und Poliklinik für Urologie
2019-2020
Institut Català d'Oncologia
2014-2016
Institut d'Investigació Biomédica de Bellvitge
2014-2016
Bellvitge University Hospital
2016
Germ cell tumors (GCT) might undergo transformation into a somatic-type malignancy (STM), resulting in fate switch to usually found somatic tissues, such as rhabdomyosarcomas or adenocarcinomas. STM is associated with poor prognosis, but the molecular and epigenetic mechanisms triggering are still enigmatic, tissue-of-origin under debate biomarkers lacking.
Abstract Meriolin derivatives represent a new class of kinase inhibitors with pronounced cytotoxic potential. Here, we investigated newly synthesized meriolin derivative (termed 16) that displayed strong apoptotic potential in Jurkat leukemia and Ramos lymphoma cells. 16 induced apoptosis rapid kinetics (within 2–3 h) more potently (IC 50 : nM) than the previously described 31 36 [1]. Exposure cells to 16, 31, or for 5 min was sufficient trigger severe irreversible cytotoxicity. Apoptosis...
Cisplatin-based regimens are routinely employed for the treatment of urothelial carcinoma. However, therapeutic success is hampered by primary presence or development cisplatin resistance. This chemoresistance executed multiple cellular pathways. In recent years, process autophagy has been identified as a prosurvival pathway cancer cells. On one hand, enables cells to survive conditions low oxygen nutrient supply, frequently found in tumors. other supports Here, we aimed at investigating...
Germ cell tumours (GCTs) are the most common solid malignancies in young men. Although high cure rates can be achieved, metastases, resistance to cisplatin-based therapy and late toxicities still represent a lethal threat, arguing for need of new therapeutic options. In this study, we analysed potential cyclin-dependent kinase 4/6 (CDK4/6) inhibitors palbociclib ribociclib (PaRi) as molecular drugs treat cisplatin-resistant -sensitive paediatric adult GCTs. Ten GCT lines, including subclones...
Background: Cell culture models of normal urothelial cells are important for studying differentiation, disease mechanisms and anticancer drug development.Beyond primary cultures with their limitations in lifespan, interindividual heterogeneity supply, few conditionally immortalized cell lines limited applicability due to partial transformation or impaired differentiation capacity available.We describe characteristics the new spontaneously line HBLAK derived from a uroepithelial...
Therapeutic efficacy of cisplatin-based treatment late stage urothelial carcinoma (UC) is limited by chemoresistance. To elucidate underlying mechanisms and to develop new approaches for overcoming resistance, we generated long-term cisplatin treated (LTT) UC cell lines, characterised their response, determined the expression molecules involved in transport detoxification, DNA repair, apoptosis. Inhibitors metallothioneins Survivin were applied investigate ability sensitise towards...
Inhibitors of the mechanistic target rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis response inhibition. This feature driven by EVI1 SOX9. functionally cooperates with positively regulates SOX9, promotes...
Abstract Yolk‐sac tumours (YSTs), a germ cell tumour subtype, occur in newborns and infants as well young adults of age 14‐44 years. In clinics, adult patients with YSTs face poor prognosis, these are often therapy‐resistant count for many related deaths. So far, the molecular (epi)genetic mechanisms that control development YST far from being understood. We deciphered regulating formation by meta‐analysing high‐throughput data gene microRNA expression, DNA methylation mutational burden....
Abstract Background Type II germ cell tumors (GCT) are the most common solid cancers in males of age 15 to 35 years. Treatment these includes cisplatin-based therapy achieving high cure rates, but also leading late toxicities. As mainly young men suffering from GCTs, toxicities play a major role regarding life expectancy, and development resistance emphasizes need for alternative therapeutic options. GCTs highly susceptible interference with epigenetic landscape; therefore, this study...
In germ cell tumors (GCT), a growing teratoma during chemotherapy with decreasing tumor markers was defined as 'growing syndrome` (GTS) by Logothetis et al., in 1982. So far, its pathogenesis and specific treatment options remain elusive. We aimed at updating the GTS definition based on molecular epigenetic features well identifying circulating biomarkers. selected 50 patients for clinical characterization subsequently 12 samples were molecularly analyzed. further included 7 longitudinal of...
Tumour heterogeneity and resistance to systemic treatment in urothelial carcinoma (UC) may arise from cancer stem cells (CSC). A recent model describes cellular differentiation states within UC based on corresponding expression of surface markers (CD) cytokeratins (CK) with CD90 CK14 positive representing the least differentiated most tumourigenic population. Based fact that this population is postulated constitute CSCs origin cisplatin resistance, we enriched cell lines (UCCs) for studied...
Abstract Background Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients present with a remaining (resistant) yolk-sac tumor (YST(-R)) component, resulting poor prognosis due to lack of novel treatment options besides and surgery. The aim this study was identify targets YST by deciphering molecular mechanisms therapy resistance. Additionally, we screened cytotoxic efficacy...
Germ cell tumors (GCT) are the most common solid in young men of age 15 - 40. In previous studies, we profiled interaction GCT cells with tumor microenvironment (TM). Earlier studies showed that especially 3D fibroblasts (FB) or macrophages influenced growth behavior and cisplatin response as well transcriptome secretome cells, suggesting crosstalk these is crucial for progression therapy outcome. this study, shed light on mechanisms activation cancer-associated (CAF) setting their effects...
Abstract Relapsing germ cell tumor (GCT) patients often harbor components of the aggressive subtype yolk‐sac (YST), suggesting that YST formation is an escape mechanism under therapy. Nevertheless, molecular mechanisms inducing development from its stem cell‐like precursor embryonal carcinoma (EC) are largely unexplored. We demonstrated induction transcription factor SOX17 together with stimulation WNT, TGF‐beta / Activin, and FGF signaling drives EC cells into lineage. Single RNA sequencing...
Cisplatin-based treatment is the standard of care therapy for urothelial carcinomas. However, complex cisplatin resistance mechanisms limit success this approach. Both apoptosis and autophagy have been shown to contribute resistance. Prodigiosin, a secondary metabolite from various bacteria, exerts different biological activities including modulation these two cellular stress response pathways. We analyzed effect prodigiosin on protein levels autophagy- apoptosis-related proteins in...
Abstract The enzyme type 1 17β‐hydroxysteroid dehydrogenase (17β‐HSD‐1), responsible for generating active 17β‐estradiol (E2) from low‐active estrone (E1), is overexpressed in endometrial cancer (EC), thus implicating an increased intra‐tissue generation of E2 this estrogen‐dependent condition. In study, we explored the possibility inhibiting 17β‐HSD‐1 and impairing E1 EC using vitro , vivo ex models. We generated cell lines derived well‐differentiated adenocarcinoma Ishikawa line expressing...
Abstract Testicular germ cell tumours (GCTs) mostly affect young men at age 17‐40. Although high cure rates can be achieved by orchiectomy and chemotherapy, GCTs still a lethal threat to patients with metastases or therapy resistance. Thus, alternative treatment options are needed. Based on studies utilising GCT lines, the histone deacetylase inhibitor romidepsin is promising therapeutic option, showing toxicity very low doses towards cisplatin‐resistant cells, but not fibroblasts Sertoli...
Cisplatin (CisPt) is frequently used in the therapy of urothelial carcinoma (UC). Its therapeutic efficacy limited by inherent or acquired drug resistance. Here, we comparatively investigated CisPt-induced response two different parental cell lines (RT-112, J-82) with that respective resistant variants (RT-112R, J-82R) obtained upon month-long CisPt selection. Parental RT-112 cells were ~2.5 fold more to than J-82 and showed a expression pattern CisPt-related resistance factors. RT-112R...
Germ cell tumors (GCTs) are the most common solid malignancies found in young men. Although they generally have high cure rates, metastases, resistance to cisplatin-based therapy, and late toxicities still represent a lethal threat, arguing for need of new therapeutic options. In previous study, we identified downregulation chromatin-remodeling SWI/SNF complex member ARID1A as key event mode action histone deacetylase inhibitor romidepsin. Additionally, loss-of-function mutations...
Alternative therapeutic options targeting urologic malignancies, such as germ cell tumours, well urothelial, renal and prostate carcinomas, are still urgently needed. The membrane protein CD24 represents a promising immunotherapeutical approach. present study aimed to decipher the molecular function of in vitro evaluate cytotoxic capacity third‐generation natural killer (NK) chimeric antigen receptor (CAR) against tumour lines. Up 20 lines several non‐malignant control cells were included....