A5053867026- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Cytokine Signaling Pathways and Interactions
- Steroid Chemistry and Biochemistry
- Histone Deacetylase Inhibitors Research
- Cancer Mechanisms and Therapy
- Hormonal and reproductive studies
- Cancer, Lipids, and Metabolism
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Radiopharmaceutical Chemistry and Applications
- Cancer-related Molecular Pathways
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Genomics and Diagnostics
- Immune Response and Inflammation
- Cancer-related gene regulation
- Protein Hydrolysis and Bioactive Peptides
- Reproductive System and Pregnancy
- PARP inhibition in cancer therapy
- Prostate Cancer Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Sexual Differentiation and Disorders
- Chemical Synthesis and Analysis
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
Innsbruck Medical University
2015-2025
Universität Innsbruck
2016-2025
KU Leuven
2018-2024
Purpose: The major obstacle in the management of advanced prostate cancer is occurrence resistance to endocrine therapy. Although androgen receptor (AR) has been linked therapy failure, underlying escape mechanisms have not fully clarified. Being closely related AR, glucocorticoid (GR) suggested play a role enzalutamide and docetaxel resistance. Given that glucocorticoids are frequently applied patients, it essential unravel exact GR progression.Experimental Design: Assessment expression...
Abstract Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond systemic therapy. Here, we employ single-cell assays for transposase-accessible chromatin (ATAC) RNA sequencing in models of early treatment response resistance enzalutamide. In doing so, identify pre-existing treatment-persistent cell subpopulations possess regenerative potential when subjected treatment. We find distinct landscapes associated with enzalutamide...
Abstract Prostate cancer progression is driven by androgen receptor (AR) activity, which a target for therapeutic approaches. Enzalutamide an AR inhibitor that prolongs the survival of patients with advanced prostate cancer. However, resistance mechanisms arise and impair its efficacy. One these expression AR-V7, constitutively active splice variant. The Mediator complex multisubunit protein modulates gene on genome-wide scale. MED12 cyclin-dependent kinase (CDK)8, or paralog CDK19, are...
Abstract Interleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels tumour microenvironment cancer patients, where concentrations correlate with grade malignancy. In prostate cancer, interleukin-4 associated activation androgen receptor, increased proliferation survival pathways such as Akt NF-κB. However, its therapy resistance not yet determined. Here we investigate influence on primary epithelial cells from patients. Our data demonstrate...
Abstract Inhibition of the androgen receptor (AR) by second-generation anti-androgens is a standard treatment for metastatic castration resistant prostate cancer (mCRPC), but it inevitably leads to development resistance. Since introduction highly efficient AR signalling inhibitors, approximately 20% mCRPC patients develop disease with independent resistance mechanisms. In this study, we generated two anti-androgen and cell models that do not rely on activity growth despite robust expression...
// Julia Hoefer 1 , Mohammady Akbor 1, 2 Florian Handle Philipp Ofer Martin Puhr Walther Parson 3, 4 Zoran Culig 5 Helmut Klocker * Isabel Heidegger Department of Urology, Division Experimental Medical University Innsbruck, Austria School Biosciences and Veterinary Medicine, Camerino, Italy 3 Institute Legal Forensic Science Program, The Pennsylvania State University, Park, Pennsylvania, USA Center Biomolecular Cellular Engineering, International Clinical Research Center, St. Anne's...
Abstract Prostate cancer that is resistant to anti-androgen treatment, such as enzalutamide, represents a therapeutic challenge. To study their molecular and functional features, the enzalutamide-resistant PCa cell lines LNCaP Abl EnzR DuCaP constitute valuable in vitro models. In this work, we explored two different strategies for reducing AR/AR-V7/c-Myc. MED12 knockdown decreased protein expression of AR, AR-V7 c-Myc. Similarly, identified AR targets miR-454-3p. Concomitantly, transfection...
Novel drugs like Abiraterone or Enzalutamide, which target androgen receptor (AR) signaling to improve deprivation therapy (ADT), have been developed during the past years. However, application of these is limited because occurrence inherent acquired resistances treatment. Thus, identification new molecular targets urgently required current therapeutic prostate cancer (PCa) treatment strategies. PIAS1 (protein inhibitor activated STAT1 (signal transducer and activator transcription-1)) known...
IL6/STAT3 signaling is associated with endocrine therapy resistance in prostate cancer, but therapies targeting this pathway cancer were unsuccessful clinical trials so far. The mechanistic explanation for phenomenon currently unclear; however, IL6 has pleiotropic effects on a number of pathways, including the androgen receptor (AR). Therefore, we investigated IL6-mediated AR activation cell lines and ex vivo primary tissue cultures order to gain better understanding how inhibit process...
Abstract The proinflammatory cytokine IL6 is associated with bad prognosis in prostate cancer and implicated progression to castration resistance. Suppressor of signaling 3 (SOCS3) an IL6-induced negative feedback regulator the IL6/Janus kinase (JAK)/STAT3 pathway. This study reveals that SOCS3 promoter hypermethylated cancerous regions compared adjacent benign tissue using methylation-specific qPCR. A series vitro experiments was performed assess functional impact low expression during...
Prostate cancer (PCa) is among the most common adult malignancies, and second leading cause of cancer-related death in men. As PCa hormone dependent, blockade androgen receptor (AR) signaling an effective therapeutic strategy for men with advanced metastatic disease. The discovery enzalutamide, a compound that effectively blocks AR axis its clinical application has led to significant improvement survival time. However, effect enzalutamide not permanent, resistance treatment ultimately leads...
Abstract Despite increasing options for treatment of castration-resistant prostate cancer, development drug resistance is inevitable. The glucocorticoid receptor (GR) a prime suspect acquired therapy resistance, as cancer (PCa) cells are able to increase GR signaling during anti-androgen and thereby circumvent androgen (AR)-blockade cell death. As standard AR-directed therapies fail block the inhibitors might result in intolerable side effects, identification signature genes, which better...
// Frédéric R. Santer 1 , Holger H. Erb 1,2 Su Jung Oh Florian Handle Gertrud E. Feiersinger Birgit Luef Huajie Bu Georg Schäfer Christian Ploner 3 Martina Egger Jayant K. Rane 2 Norman J. Maitland Helmut Klocker Iris Eder 1,* and Zoran Culig Medical University of Innsbruck, Department Urology, Division Experimental Austria Yorkshire Cancer Research Unit, York, United Kingdom Plastic, Reconstructive & Aesthetic Surgery, * Joint senior authors Correspondence to: Culig, email: Keywords :...
Prostate cancer (PCa) is one of the most frequently diagnosed tumors in men. In general, therapies for localized PCa are curative. However, treatment advanced considered palliative since development therapy resistance occurs rapidly. It has been shown that tumor-initiating cells likely involved resistance. They not eliminated by conventional and thereby lead to tumor progression relapse. The aim this study was evaluate effects known stem cell inhibitor salinomycin on critical subpopulation...
Patients with advanced prostate cancer are frequently treated the antiandrogen enzalutamide. However, resistance eventually develops in virtually all patients, and various mechanisms have been associated this process. The histone acetyltransferases EP300 CREBBP involved regulation of cellular events cancer. This study investigated role EP300/CREBBP inhibitors enzalutamide-resistant led to same inhibition androgen receptor activity -sensitive cells. cells were more sensitive these viability...
Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, angiogenesis PCa. To identify novel pathways that triggered by IL6, we performed a gene expression profiling two PCa cell lines, LNCaP MDA 2b, treated 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one the most prevalent IL6-regulated genes in both lines. IRF9 is mediator type I IFN...
Administration of the microtubule inhibitor docetaxel is a common treatment for metastatic castration-resistant prostate cancer (mCRPC) and results in prolonged patient overall survival. Usually, after short period time chemotherapy resistance emerges there urgent need to find new therapeutic targets overcome therapy resistance. The lysine-acetyltransferase p300 has been correlated (PCa) progression. Here, we aimed clarify possible function verify as target chemoresistant PCa....
Abstract Despite significant therapeutic advances in recent years, treatment of metastatic prostate cancer (PCa) remains palliative, owing to the inevitable occurrence drug resistance. There is increasing evidence that epithelial glucocorticoid receptor (GR) signaling and changes tumor-microenvironment (TME) play important roles this process. Since glucocorticoids (GCs) are used as concomitant medications course PCa treatment, it essential investigate impact GCs on stromal GR TME. Therefore,...
The atypical protein kinase/ATPase RIO kinase (RIOK)-1 is involved in pre-40S ribosomal subunit production, cell-cycle progression, and arginine N-methyltransferase 5 methylosome substrate recruitment. RIOK1 overexpression a characteristic of several malignancies correlated with cancer stage, therapy resistance, poor patient survival, other prognostic factors. However, its role prostate (PCa) unknown. In this study, the expression, regulation, therapeutic potential PCa were examined. mRNA...
Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and granulation tissue, type premature tissue without epithelialization. Regenerative cells from wound periphery contribute healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated microenvironment.We examined CD45-/CD31-/CD34+ preadipocytes CD68+...
We investigate the use of a frequency-domain reconstruction algorithm based on nonuniform fast Fourier transform (NUFFT) for photoacoustic imaging (PAI). Standard algorithms (FFT) are computationally efficient, but compromise image quality by artifacts. In our previous work we have developed an PAI NUFFT which is efficient and can reconstruct images with known from temporal backprojection algorithms. this paper review qualities, such as resolution, signal-to-noise ratio, effects artifacts in...
Despite enzalutamide's efficacy in delaying the progression of metastatic castration-resistant prostate cancer (CRPC), resistance to this anti-androgen inevitably occurs. Several studies have revealed that signal transducer and activator transcription (STAT) 5 plays a role tumour development drug such as enzalutamide. Data mining heterogeneous expression STAT5 enzalutamide-treated mCRPC patients enzalutamide-resistant (PCa). Isobologram analysis inhibitor pimozide combined with enzalutamide...