Search results for "blas"
showing 10 items of 2217 documents
Bmi1 and Cell of Origin Determinants of Brain Tumor Phenotype
2007
Glioblastomas frequently express oncogenic EGFR and loss of the Ink4a/Arf locus. Bmi1, a positive regulator of stem cell self renewal, may be critical to drive brain tumor growth. In this issue of Cancer Cell, Bruggeman and colleagues suggest that brain tumors with these molecular alterations can be initiated in both neural precursor and differentiated cell compartments in the absence of Bmi1; however, tumorigenicity is reduced, and tumors contain fewer precursor cells. Surprisingly, tumors appear less malignant when initiated in precursor cells. Bmi1-deficient tumors also had fewer neuronal lineage cells, suggesting a role for Bmi1 in determination of cell lineage and tumor phenotype.
RB acute loss induces centrosome amplification and aneuploidy in murine primary fibroblasts
2006
AbstractBackgroundIncorrect segregation of whole chromosomes or parts of chromosome leads to aneuploidy commonly observed in cancer. The correct centrosome duplication, assuring assembly of a bipolar mitotic spindle, is essential for chromosome segregation fidelity and preventing aneuploidy. Alteration of p53 and pRb functions by expression of HPV16-E6 and E7 oncoproteins has been associated with centrosome amplification. However, these last findings could be the result of targeting cellular proteins in addition to pRb by HPV16-E7 oncoprotein. To get a more detailed picture on the role of pRb in chromosomal instability and centrosome amplification, we analyzed the effects of the acute loss …
Partial restoration of pre-transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants.
1995
Neoplastic transformation mediated by ras oncogenes is associated with deregulated expression of genes encoding, for example, various proteases, lysyl oxidase, and smooth-muscle α-actin. To define the role of these genes in the initiation or maintenance of the ras-transformed state, we compared their steady-state mRNA levels in two different sets of preneoplastic fibroblast lines, ras-transformed clones, and phenotypic revertants derived from them. Compared with the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix metalloproteinase–3), and collagenase I (matrix metalloproteinase–1) mR…
pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-…
2003
The estrogen receptor-alpha (ER) plays a crucial role in normal breast development and is also linked to development and progression of mammary carcinoma. The transcriptional repression of ER-alpha gene in breast cancer is an area of active investigation with potential clinical significance. However, the molecular mechanisms that regulate the ER-alpha gene expression are not fully understood. Here we show a new molecular mechanism of ER-alpha gene inactivation mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between p…
Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription
2003
AbstractRecent efforts to develop pharmacologic agents that restore function to mutant forms of p53 hold significant promise in cancer therapy. Here, we examine the effects of such pharmacologic activation of p53 function using a small molecule, PRIMA-1, and a model system employing a p53 protein fused to a mutant steroid binding domain of the murine estrogen receptor (p53ERtam) that renders it responsive only in the presence of 4-hydroxytamoxifen. In either case, p53 activation triggered apoptosis that was not inhibited by the presence of macromolecular synthesis inhibitors. This p53-induced, transcription-independent apoptosis is Bax dependent, proceeds in the absence of a nucleus, and in…
Heat-Shock Proteins in Sea Urchin Embryos
1982
The production of heat-shock proteins in sea urchin embryos is accompanied by the appearance at the polysomal level of their relative mRNAs, as shown by their translation in a cell-free system; thus suggesting that the regulation of their production occurs at a transcriptional level. The mechanism for the inhibition of the bulk protein synthesis and for its reversal on the other hand should be looked for at a posttranscriptional level, since both these phenomena occur also in the presence of actinomycin D. The heat-shock proteins produced as early as at the mesenchyme blastula stage persist within the embryo at least till the pluteus stage.
Lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC): Phase 3 LEA…
2019
TPS4152 Background: Len, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, is approved for first-line treatment of unresectable HCC (uHCC) based on the open-label phase 3 REFLECT study in which len showed noninferior overall survival (OS) and significantly improved objective response rate (ORR), progression-free survival (PFS), and time-to-progression (TTP) vs sorafenib. In the phase 2 KEYNOTE-224 study of pembro (a PD-1 inhibitor) as second-line treatment of advanced HCC, pembro showed meaningful clinical efficacy in pts previously treated with sorafenib, with median PFS 4.9 mo, median OS 12.9 mo, and a manageable safety profile. In results from the pha…
RNA-sequencing and bioinformatic analysis to pre-assess sensitivity to targeted therapeutics in recurrent glioblastoma.
2019
e13533 Background: This study developed molecular guided tools for individualized selection of chemotherapeutics for recurrent glioblastoma (rGB). A consortium involving clinical neurooncologists, molecular biologists and bioinformaticians identified gene expression patterns in rGB and quantitatively analyzed pathways involved in response to FDA approved oncodrugs. Methods: From2016 to 2018 biopsies from GB were collected using a multisampling approach. Biopsy material was used to isolate glioma stem-like cells and examined by RNA-sequencing. RNA-seq results were subjected to differential expression (DE) analysis and Oncobox analysis – a bioinformatic tool for quantitative pathway activati…
Neuroblastoma with MYCN amplification plus 11q deletion: immunohistochemical expression of angiogenic factors
2010
Neuroblastoma (NB) is an extra-cranial solid neoplasm in childhood. Genetic markers as MYCN amplification (MNA) and deletion of 11q (11q ) are considered factors with an adverse prognosis. Usually, an inverse relationship between MNA and 11q is found. Approximately 13% of the MNA cases present with 11q . These cases show a dramatic decline in survival rates. Hypoxia-inducible factor-2a (HIF-2a) protein expression has been described as an indicator of poor outcome, has been correlated with an aggressive phenotype in NB, and serves as a marker for stem cell-like phenotypes. Additionally, HIF-2a positive cells strongly express vascular endothelial growth factor (VEGF) and, as such, could be in…
Geranylgeraniol - a new potential therapeutic approach to bisphosphonate associated osteonecrosis of the jaw.
2010
Bisphosphonate associated osteonecrosis of the jaw (BP-ONJ) is one of the main side effects of bisphosphonate therapy (BPT). To date, there is no effective therapy of the BP-ONJ. Nitrogen-containing bisphosphonates (N-BPs) are particularly able to inhibit pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). Consequent of decreased synthesis of the metabolite Geranylgeraniol (GGOH) is believed to largely account for the development of BP-ONJ. Negative effect of N-BPs could be shown, resulting in decreased viability and migration capacity of different cell types of hard and soft tissues such as osteoblasts, fibroblast und endothelial cells. Aim of our in vitro study was to demonstra…