Protein profile of basal prostate epithelial progenitor cells--stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo.
Journal of Cellular and Molecular Medicine 20(4):721 (2016)
The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-ph...
CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma.
Nature Medicine 22(3):278 (2016)
Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-lik...
The influence of prostatic anatomy and neurotrophins on basal prostate epithelial progenitor cells.
Prostate 76(1):114 (2016)
Based on findings of surface marker, protein screens as well as the postulated near-urethral location of the prostate stem cell niche, we were interested whether androgen ablation, distinct anatomic regions within the prostate or neurotrophins have an influence on basal prostate epithelial proge...
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.
Cell 162(1):146 (2015)
KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
Defined conditions for the isolation and expansion of basal prostate progenitor cells of mouse and human origin.
Stem cell reports 4(3):503 (2015)
Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs) have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse ba...
Bortezomib sensitizes primary meningioma cells to TRAIL-induced apoptosis by enhancing formation of the death-inducing signaling complex.
Journal of Neuropathology & Experimental Neurology 73(11):1034 (2014)
A meningioma is the most common primary intracranial tumor in adults. Here, we investigated the therapeutic potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in 37 meningiomas. Freshly isolated primary meningioma cells were treated with TRAIL with or without differ...
Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy.
Urologic Oncology: Seminars and Original Invest... 32(5):678 (2014)
To evaluate CD24/CD44/CD47 cancer stem cell marker expressions in bladder cancer (BCa) and provide data on their prognostic significance for clinical outcome in patients undergoing radical cystectomy (RC).
Primary BCa tissue was used for xenograft studies. A tissue microarray was prepared using ...
Development and characteristics of preclinical experimental models for the research of rare neuroendocrine bladder cancer.
The Journal of Urology 190(6):2263 (2013)
For rare cancers such as neuroendocrine bladder cancer treatment options are limited due partly to the lack of preclinical models. Techniques to amplify rare primary neuroendocrine bladder cancer cells could provide novel tools for the discovery of drug and diagnostic targets. We developed precl...
Potential role of soluble TRAIL in epithelial injury in children with severe RSV infection.
American Journal of Respiratory Cell and Molecu... 42(6):697 (2010)
Lower respiratory tract infection by respiratory syncytial virus (RSV) is a frequent cause of acute lung injury in young children and infants. Studies in adults and animals suggest that tumor necrosis factor receptor (TNFR) ligands may mediate lung injury by causing apoptosis of epithelial cells...
Oncogenic K-Ras turns death receptors into metastasis-promoting receptors in human and mouse colorectal cancer cells.
Gastroenterology 138(7):2357 (2010)
Death receptors expressed on tumor cells can prevent metastasis formation by inducing apoptosis, but they also can promote migration and invasion. The determinants of death receptor signaling output are poorly defined. Here we investigated the role of oncogenic K-Ras in determining death recepto...
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.
Nature Cell Biology 12(5):468 (2010)
Despite the presence of mutations in APC or beta-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when beta-catenin localization is analysed, indicating a more complex regulation of Wnt signalling. We explored ...
The AC133 epitope, but not the CD133 protein, is lost upon cancer stem cell differentiation.
Cancer Research 70(2):719 (2010)
Colon cancer stem cells (CSC) can be identified with AC133, an antibody that detects an epitope on CD133. However, recent evidence suggests that expression of CD133 is not restricted to CSCs, but is also expressed on differentiated tumor cells. Intriguingly, we observed that detection of the AC1...
Tumor microvasculature supports proliferation and expansion of glioma-propagating cells.
International Journal of Cancer 125(5):1222 (2009)
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The identification of 'cancer stem cells' (CSC) has shed new light on the potential mechanism of therapy resistance of these tumors. Because these cells appear to be more resistant to conventional treatments, th...
One renegade cancer stem cell?
Cell Cycle 8(6):803 (2009)
The CSC compartment represents the subpopulation of tumor cells with clonogenic potential and the ability to initiate new tumors. Besides self renewal, one of their main features is their ability to differentiate into the variety of cells within the tumor. The question remains whether this poten...
NF-kappaB inhibition reveals differential mechanisms of TNF versus TRAIL-induced apoptosis upstream or at the level of caspase-8 activation independent of cIAP2.
Journal of Investigative Dermatology 128(5):1134 (2008)
Death ligands not only activate a death program but also regulate inflammatory signalling pathways, for example, through NF-kappaB induction. Although tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TNF both activate NF-kappaB in human keratinocytes, only TRAIL potently...
Bortezomib sensitizes primary human astrocytoma cells of WHO grades I to IV for tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.
Clinical Cancer Research 13(11):3403 (2007)
Malignant gliomas are the most aggressive human brain tumors without any curative treatment. The antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in gliomas has thus far only been thoroughly established in tumor cell lines. In the present study, we investigated...
TRAIL/bortezomib cotreatment is potentially hepatotoxic but induces cancer-specific apoptosis within a therapeutic window.
Hepatology 45(3):649 (2007)
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a novel promising anticancer biotherapeutic. However, TRAIL-resistant tumor cells require combinatorial regimens to sensitize tumor but not normal cells for TRAIL-induced apoptosis. Here, we investigated the mechanism of ...
The interplay between the Bcl-2 family and death receptor-mediated apoptosis.
Biochimica et Biophysica Acta 1644(2-3):125 (2004)
Two principal pathways for apoptosis initiation exist. One pathway, which is also termed the 'extrinsic' pathway, is mediated by death receptors, a subgroup of the TNF receptor superfamily. The second pathway, which is also referred to as the 'intrinsic' pathway is controlled by members of the B...
TRAIL-induced apoptosis and gene induction in HaCaT keratinocytes: differential contribution of TRAIL receptors 1 and 2.
Journal of Investigative Dermatology 121(1):149 (2003)
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) exerts a potent cytotoxic activity especially against many tumor cell types such as transformed keratinocytes. The specific role of the different TRAIL receptors in this process, however, is unknown. In this report we examine the ro...
TNF-related apoptosis-inducing ligand mediates tumoricidal activity of human monocytes stimulated by Newcastle disease virus.
Journal of Immunology 170(4):1814 (2003)
The Newcastle disease virus (NDV) has antineoplastic and immunostimulatory properties, and it is currently clinically tested in anticancer therapy. However, the tumoricidal mechanisms of NDV tumor therapy are not fully understood. The results presented here demonstrate that NDV-stimulated human ...