Search results for "Neoplastic"
showing 10 items of 2901 documents
Targeting human {gamma}delta} T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer.
2007
Abstract The increasing evidence that γδ T cells have potent antitumor activity suggests their value in immunotherapy, particularly in areas of unmet need such as metastatic carcinoma. To this end, we initiated a phase I clinical trial in metastatic hormone-refractory prostate cancer to examine the feasibility and consequences of using the γδ T-cell agonist zoledronate, either alone or in combination with low-dose interleukin 2 (IL-2), to activate peripheral blood γδ cells. Nine patients were enlisted to each arm. Neither treatment showed appreciable toxicity. Most patients were treated with zoledronate + IL-2, but conversely only two treated with zoledronate displayed a significant long-te…
Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells
2015
Abstract Background Apoptosis and other forms of cell death have been intensively investigated in the past years to explain the mode of action of synthetic anticancer drugs and natural products. Recently, a new form of cell death emerged, which was termed ferroptosis, because it depends on intracellular iron. Here, the role of genes involved in iron metabolism and homeostasis for the cytotoxicity of ten artemisinin derivatives have been systematically investigated. Material and methods Log10IC50 values of 10 artemisinin derivatives (artesunate, artemether, arteether, artenimol, artemisitene, arteanuin B, another monomeric artemisinin derivative and three artemisinin dimer molecules) were co…
Novel isatin-derived molecules activate p53 via interference with Mdm2 to promote apoptosis
2018
International audience; The p53 protein is a key tumor suppressor in mammals. In response to various forms of genotoxic stress p53 stimulates expression of genes whose products induce cell cycle arrest and/or apoptosis. An E3-ubiquitin ligase, Mdm2 (mouse-double-minute 2) and its human ortholog Hdm2, physically interact with the amino-terminus of p53 to mediate its ubiquitin-mediated degradation via the proteasome. Thus, pharmacological inhibition of the p53-Mdm2 interaction leads to overall stabilization of p53 and stimulation of its anti-tumorigenic activity. In this study we characterize the biological effects of a novel class of non-genotoxic isatin Schiff and Mannich base derivatives (…
Cigarette smoke affects the onco-suppressor DAB2IP expression in bronchial epithelial cells of COPD patients
2019
AbstractCigarette smoke is a risk factor for COPD and lung cancer. In cancer, epigenetic modifications affect the expression of Enhancer of Zester Homolog 2 (EZH2), and silenced disabled homolog 2 interacting protein gene (DAB2IP) (onco-suppressor gene) by Histone H3 tri-methylation in lysine 27 (H3K27me3). In“ex vivo”studies, we assessed EZH2, H3K27me3 and DAB2IP immunoreactivity in bronchial epithelial cells from COPD patients (smokers, ex-smokers), Smoker and control subjects. In“in vitro” experiments we studied the effect of cigarette smoke extract (CSE) on EZH2/H3K27me3/DAB2IP expression, apoptosis, invasiveness, and vimentin expression in 16HBE, primary cells, and lung cancer cell lin…
Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice
2008
Summary Telomerase confers limitless proliferative potential to most human cells through its ability to elongate telomeres, the natural ends of chromosomes, which otherwise would undergo progressive attrition and eventually compromise cell viability. However, the role of telomerase in organismal aging has remained unaddressed, in part because of the cancer-promoting activity of telomerase. To circumvent this problem, we have constitutively expressed telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice engineered to be cancer resistant by means of enhanced expression of the tumor suppressors p53, p16, and p19ARF. In this context, TERT overexpression improves …
An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated an…
2009
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5-year survival rate. alpha-Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to alpha-enolase. The present work was intended to assess the ability of alpha-enolase to induce antigen-specific T cell responses. We show that alpha-enolase-pulsed dendritic cells (DC) specifically stimulate healt…
Do nonmelanoma skin cancers develop from extra-cutaneous stem cells?
2008
A hypothesis is presented that nonmelanoma skin cancers can develop from extra-cutaneous stem cells, and not exclusively from skin keratinocytes. This idea is supported by recent findings regarding the initiation of cancers in the digestive tract, and by a cancer stem cell model of a neoplasia. It is known that multipotent adult progenitor cells can trans-differentiate into very diverse cellular lineages and can be recruited to areas of profound tissue injury. In these settings, they might also initiate malignant transformation. Some epidemiological data and recent findings regarding mechanisms of wound healing indicate that skin cancers could also originate from bone marrow-derived or othe…
Identification of avarol derivatives as potential antipsoriatic drugs using an in vitro model for keratinocyte growth and differentiation.
2006
Contains fulltext : 49512schalkwijk.pdf (Publisher’s version ) (Closed access) Avarol, a marine sesquiterpenoid hydroquinone, and 14 avarol derivatives have shown interesting anti-inflammatory properties in previous studies. In this study, avarol and derivatives were evaluated in high-throughput keratinocyte culture models using cytokeratin 10 and SKALP/Elafin expression as markers for respectively normal and psoriatic differentiation. Avarol and five of its derivatives (5, 10, 13, 14 and 15) were selected for further study. Only 10, 13, 14 and 15 were able to inhibit keratinocyte cell growth. Changes in expression levels of 22 genes were assessed by quantitative real time PCR (qPCR). From …
Genetic ablation of mast cells redefines the role of mast cells in skin wound healing and bleomycin-induced fibrosis.
2014
Conclusive evidence for the impact of mast cells (MCs) in skin repair is still lacking. Studies in mice examining the role of MC function in the physiology and pathology of skin regenerative processes have obtained contradictory results. To clarify the specific role of MCs in regenerative conditions, here we used a recently developed genetic mouse model that allows conditional MC ablation to examine MC-specific functions in skin. This mouse model is based on the cell type–specific expression of Cre recombinase in connective tissue–type MCs under control of the Mcpt5 promoter and the Cre-inducible diphtheria toxin receptor–mediated cell lineage ablation by diphtheria toxin. In response to ex…
Rottlerin induces a transformed phenotype in human keratinocytes.
2001
PKCdelta plays a fundamental role in cell cycle control. Consistent with its proposed tumour suppressor function, ras transfection of the human keratinocyte cell line HaCaT results in a loss of PKCdelta expression mediated by TGFalpha (Exp. Cell Res., 219, 299, 1995). To get more insight into the role of PKCdelta in keratinocytes, we investigated the effects of Rottlerin, a specific inhibitor of protein kinase Cdelta, in HaCaT cells. After Rottlerin treatment, HaCaT cells lost their cobble-stone morphology and displayed a spindle-shaped, fibroblastic phenotype. Additionally, the establishment of cell-cell contacts was prevented. This was caused by an internalization of E-cadherin and beta-c…