A5053106363- Prostate Cancer Treatment and Research
- Cancer Cells and Metastasis
- Cancer-related molecular mechanisms research
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
- Tannin, Tannase and Anticancer Activities
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Steroid Chemistry and Biochemistry
- Protein Degradation and Inhibitors
- MicroRNA in disease regulation
- RNA Research and Splicing
- Cancer, Lipids, and Metabolism
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Cholesterol and Lipid Metabolism
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Molecular Biology Techniques and Applications
- Circular RNAs in diseases
- Cancer-related gene regulation
Università della Svizzera italiana
2017-2024
Institute of Oncology Research
2015-2024
Scuola Cantonale di Commercio Bellinzona
2015
University of Bern
1997-2013
University of Insubria
2012-2013
University Hospital of Bern
2012-2013
Fondazione Edo ed Elvo Tempia
2012-2013
University of Zurich
2008-2012
Mylan (Switzerland)
2012
MultiMedica
2012
Prosenescence therapy has recently emerged as a novel therapeutic approach for treating cancer. However, this concept is challenged by conflicting evidence showing that the senescence-associated secretory phenotype (SASP) of senescent tumor cells can have pro- well antitumorigenic effects. Herein, we report that, in Pten-null tumors, activation Jak2/Stat3 pathway establishes an immunosuppressive microenvironment contributes to growth and chemoresistance. Activation tumors sustained...
Abstract Human melanoma is composed of distinct cell types reminiscent neural crest derivatives and contains multipotent cells that express the stem markers CD271(p75NTR) Sox10. When isolated from solid tumors by using a method leaves intact surface epitopes, CD271-positive, but not CD271-negative, formed on transplantation into nude or nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. These fully mirrored heterogeneity parental could be passaged more than 5 times. In...
Wnt and Notch signaling have long been established as strongly oncogenic in the mouse mammary gland. Aberrant expression of several Wnts other components this pathway human breast carcinomas has reported, but evidence for a causative role disease missing. Here we report that increased signaling, achieved by ectopic Wnt-1, triggers DNA damage response (DDR) an ensuing cascade events resulting tumorigenic conversion primary epithelial cells. Wnt-1-transformed cells high telomerase activity...
New discoveries in RNA biology underscore a need for chemical tools to clarify their roles pathophysiological mechanisms. In certain cancers, synthesis of the let-7 microRNA tumor suppressor is blocked by an binding protein (RBP) Lin28, which docks onto conserved sequence precursor molecules and prevents maturation. Thus, Lin28/let-7 interaction might be attractive drug target, if not well-known difficulty targeting RNA-protein interactions with drugs. Here, we describe protein/RNA FRET...
Cancer stem cells (CSC) play a significant role in tumor progression, disease recurrence, and treatment failure. Here, we show that the endogenously expressed ETS transcription factor ESE3/EHF controls prostate epithelial cell differentiation stem-like potential. We found loss of induced epithelial-to-mesenchymal transition (EMT), features, tumor-initiating metastatic properties cells, reexpression inhibited tumorigenic potential cancer cells. Mechanistically, repressed expression key EMT...
Significance The transcription factor STAT3 is involved in multiple oncogenic signaling pathways and an attractive therapeutic target. This study shows that a potent inhibitor of interferes with mitochondrial activity protein homeostasis, leading to synthetic lethality effect glucose-depleted cancer cells. These findings provide rationale for novel strategies based on the use inhibitors treatment.
LONG-TERM treatment of astrocytes in primary culture with L-glutamate (0.1–3 mM) resulted a dose-dependent increase D-[3H]aspartate uptake. The effect was abolished by an antagonist kainate/AMPA receptors, CNQX, and mimicked kainate, but not AMPA or tACPD. Both glutamate kainate caused dramatic up-regulation (82% 69%, respectively) GLAST, predominant transporter cultured astroglia, though the mRNA levels appeared unaffected. Long-term cultures dBcAMP stimulated uptake as well GLAST...
Several studies link disease progression, recurrence, and treatment failures to the cancer stem-like cell (CSC) subpopulation within heterogeneous tumor population. Myc is a transcription factor having central function in stem biology human cancers. Hence, represents an attractive target develop CSC-specific therapies. Recent findings suggest that can be silenced using RNA interference (RNAi)-based strategy targets noncoding promoter-associated (paRNA) overlapping start site. In this study,...
Chromosomal translocations leading to deregulated expression of ETS transcription factors are frequent in prostate tumors. Here, we report a novel mechanism oncogenic activation the factor ESE1/ELF3 was overexpressed human primary and metastatic It mediated transforming phenotypes vitro vivo induced an inflammatory transcriptome with changes relevant pathways. by interleukin (IL)-1β through NF-κB crucial mediator phenotypic transcriptional IL-1β cancer cells. This linkage interaction...
Mutations and deletions in components of ubiquitin ligase complexes that lead to alterations protein turnover are important mechanisms driving tumorigenesis. Here we describe an alternative mechanism involving upregulation the microRNA miR-424 leads impaired ubiquitination degradation oncogenic transcription factors prostate cancers. We found targets E3 COP1 identified STAT3 as a key substrate promoting tumorigenic cancer stem-like properties epithelial cells. Altered due function led...
Abstract Although cancer stem-like cells (CSC) are thought to be the most tumorigenic, metastatic, and therapy-resistant cell subpopulation within human tumors, current therapies target bulk tumor while tending spare CSC. In seeking understand mechanisms needed acquire maintain a CSC phenotype in prostate cancer, we investigated connections between ETS transcription factor ESE3/EHF, Lin28/let-7 microRNA axis, this malignancy. normal cells, found that ESE3/EHF bound repressed promoters for...
Extracellular vesicles (EVs) are relevant means for transferring signals across cells and facilitate propagation of oncogenic stimuli promoting disease evolution metastatic spread in cancer patients. Here, we investigated the release miR-424 circulating small EVs or exosomes from prostate patients assessed functional implications multiple experimental models. We found higher frequency positive with compared to primary tumors BPH. Release was enhanced cell lines (LNCaPabl), transgenic mice...
Using microdialysis and a sensitive RIA, we have studied the in vivo release of neuropeptide galanin (GAL) from ventral hippocampus freely moving rats. The spontaneous outflow GAL-like immunoreactivity (GAL-LI) (1.8 +/- 0.3 fmol per ml 20 min) was dependent on presence extracellular Ca2+ inhibited by tetrodotoxin. Evoked induced infusion KCl (60 mM) or veratridine (148 microM) also Ca(2+)-dependent to Electrical stimulation limb diagonal band nuclei frequency-dependent (50-200 Hz)...
Recent molecular studies provide evidence for a significant transcriptional plasticity of tumor cell subpopulations that facilitate an active contribution to vasculature. This feature is accompanied by morphological changes both in vitro and vivo. Herein, we investigated the cells with special focus on vasculogenic mimicry neovascularisation human melanoma mouse xenografts lines. In xenograft experiments, different vessel markers green fluorescent protein expression were used show how...
Abstract Cancer stem cells (CSC) contribute to disease progression and treatment failure in prostate cancer because of their intrinsic resistance current therapies. The transcription factors NF-κB STAT3 are frequently activated advanced sustain expansion CSCs. EC-70124 is a novel chimeric indolocarbazole compound generated by metabolic engineering the biosynthetic pathways glycosylated indolocarbazoles, such as staurosporine rebeccamycin. In vitro kinome analyses revealed that acted...
// Domenico Albino 1, 2 , Gianluca Civenni Simona Rossi Abhishek Mitra Carlo V. Catapano 2, 3 Giuseppina M. Carbone 1 Tumor Biology and Experimental Therapeutics Program, Institute of Oncology Research (IOR), Bellinzona, Switzerland Southern (IOSI), Department Oncology, Faculty Medicine, University Lausanne, Correspondence to: Carbone, email: pina.carbone@ior.iosi.ch Keywords: ETS transcription factor, ESE3/EHF, IL-6, cancer stem cells, prostate Received: July 15, 2016 Accepted: October 03,...
Abstract The TMPRSS2-ERG gene fusion is the most frequent alteration observed in human prostate cancer. However, its role disease progression still unclear. In this study, we uncover an important mechanism promoting ERG oncogenic activity. We show that methylated by Enhancer of zest homolog 2 (EZH2) at a specific lysine residue (K362) located within internal auto-inhibitory domain. Mechanistically, K362 methylation modifies intra-domain interactions, favors DNA binding and enhances...
Castration-resistant prostate cancer (CRPC) is a frequently occurring disease with adverse clinical outcomes and limited therapeutic options. Here, we identify methionine adenosyltransferase 2a (MAT2A) as critical driver of the androgen-indifferent state in ERG fusion-positive CRPC. MAT2A upregulated CRPC cooperates promoting cell plasticity, stemness tumorigenesis. RNA, ATAC ChIP-sequencing coupled histone post-translational modification analysis by mass spectrometry show that broadly...