Search results for "asm"
showing 10 items of 16598 documents
Repurposing of plant alkaloids for cancer therapy: Pharmacology and toxicology.
2019
Drug repurposing (or repositioning) is an emerging concept to use old drugs for new treatment indications. Phytochemicals isolated from medicinal plants have been largely neglected in this context, although their pharmacological activities have been well investigated in the past, and they may have considerable potentials for repositioning. A grand number of plant alkaloids inhibit syngeneic or xenograft tumor growth in vivo. Molecular modes of action in cancer cells include induction of cell cycle arrest, intrinsic and extrinsic apoptosis, autophagy, inhibition of angiogenesis and glycolysis, stress and anti-inflammatory responses, regulation of immune functions, cellular differentiation, a…
Concepts to Target MYC in Pancreatic Cancer.
2016
Abstract Current data suggest that MYC is an important signaling hub and driver in pancreatic ductal adenocarcinoma (PDAC), a tumor entity with a strikingly poor prognosis. No targeted therapies with a meaningful clinical impact were successfully developed against PDAC so far. This points to the need to establish novel concepts targeting the relevant drivers of PDAC, like KRAS or MYC. Here, we discuss recent developments of direct or indirect MYC inhibitors and their potential mode of action in PDAC. Mol Cancer Ther; 15(8); 1792–8. ©2016 AACR.
Preclinical models for precision oncology
2018
Precision medicine approaches have revolutionized oncology. Personalized treatments require not only identification of the driving molecular alterations, but also development of targeted therapies and diagnostic tests to identify the appropriate patient populations for clinical trials and subsequent therapeutic implementation. Preclinical in vitro and in vivo models are widely used to predict efficacy of newly developed treatments. Here we discuss whether, and to what extent, preclinical models including cell lines, organoids and tumorgrafts recapitulate key features of human tumors. The potential of preclinical models to anticipate treatment efficacy and clinical benefit is also presented,…
The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma…
2015
Abstract Secreted protein acidic and rich in cysteine (SPARC) is a multi-functional protein which modulates cell-cell and cell-matrix interactions. In cancer cells, SPARC behaves as a tumor promoter in a number of tumors, but it can also act as a tumor suppressor factor. Our previous results showed that the synthetic cannabinoid WIN55,212-2 (WIN), a potent cannabinoid receptor agonist, is able to sensitize osteosarcoma MG63 cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis which is accompanied with endoplasmic reticulum (ER)-stress induction and the increase in autophagic markers. In the present investigation, we studied the role of SPARC in WIN/TRAIL-induced apoptosi…
Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells
2019
To fight resistances to radiotherapy, the understanding of escape mechanisms of tumor cells is crucial. The aim of this study was to identify phosphoproteins that are regulated upon irradiation. The comparative analysis of the phosphoproteome before and after irradiation brought nucleophosmin (NPM1) into focus as a versatile phosphoprotein that has already been associated with tumorigenesis. We could show that knockdown of NPM1 significantly reduces tumor cell survival after irradiation. NPM1 is dephosphorylated stepwise within 1 hour after irradiation at two of its major phosphorylation sites: threonine-199 and threonine-234/237. This dephosphorylation is not the result of a fast cell cycl…
Molecular Engineering Strategies Tailoring the Apoptotic Response to a MET Therapeutic Antibody
2020
The MET oncogene encodes a tyrosine kinase receptor involved in the control of a complex network of biological responses that include protection from apoptosis and stimulation of cell growth during embryogenesis, tissue regeneration, and cancer progression. We previously developed an antagonist antibody (DN30) inducing the physical removal of the receptor from the cell surface and resulting in suppression of the biological responses to MET. In its bivalent form, the antibody displayed a residual agonist activity, due to dimerization of the lingering receptors, and partial activation of the downstream signaling cascade. The balance between the two opposing activities is variable in different…
HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer.
2015
Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We fur…
Colorectal Cancer Cell Line SW480 and SW620 Released Extravascular Vesicles: Focus on Hypoxia-induced Surface Proteome Changes
2018
Background/aim Extravascular vesicle (EV) proteome closely reflects the proteome of the cell of origin. Therefore, cancer cell-derived EV proteomic analysis could help in identifying cancer biomarkers. This study's goal was to investigate hypoxia-induced proteomic changes in EV released from hypoxic human isogenic non-metastatic colorectal cancer cells SW480 and metastatic colorectal cancer cells SW620. Materials and methods EV were characterized by western blot, transmission electron microscopy, proteomic analysis using liquid chromatography time-of-flight-mass spectrometry and quantified by an label-free intensity-based absolute quantitation (iBAQ) approach. Results A total of 16 proteins…
Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency
2018
In response to iron deficiency, the budding yeast Saccharomyces cerevisiae undergoes a metabolic remodeling in order to optimize iron utilization. The tandem zinc finger (TZF)-containing protein Cth2 plays a critical role in this adaptation by binding and promoting the degradation of multiple mRNAs that contain AU-rich elements (AREs). Here, we demonstrate that Cth2 also functions as a translational repressor of its target mRNAs. By complementary approaches, we demonstrate that Cth2 protein inhibits the translation of SDH4, which encodes a subunit of succinate dehydrogenase, and CTH2 mRNAs in response to iron depletion. Both the AREs within SDH4 and CTH2 transcripts, and the Cth2 TZF are es…
Comparative analysis of the effects of a sphingosine kinase inhibitor to temozolomide and radiation treatment on glioblastoma cell lines.
2017
ABSTRACT Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity. We analyzed the effect of SKI singular versus combined treat…