Search results for "AMPLIFICATION"

Aurora-A Transcriptional Silencing and Vincristine Treatment Show a Synergistic Effect in Human Tumor Cells

2008

Aurora-A is a centrosome-associated serine/threonine kinase that is overexpressed in multiple types of human tumors. Primarily, Aurora-A functions in centrosome maturation and mitotic spindle assembly. Overexpression of Aurora-A induces centrosome amplification and G 2 /M cell cycle progression. Recently, it was observed that overexpression of Aurora-A renders cells resistant to cisplatin (CDDP)-, etoposide-, and paclitaxel-induced apoptosis.Our results indicate that already in initial stages of cancer progression Aurora-A overexpression could have a major role in inducing supernumerary centrosomes and aneuploidy, as shown by immunohistochemistry on tissue sections from various stages of hu…

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 …

Gene Amplification-Associated Overexpression of the Selenoprotein tRNA Enzyme TRIT1 Confers Sensitivity to Arsenic Trioxide in Small-Cell Lung Cancer

2021

Simple Summary Small-cell lung cancer accounts for approximately 13% of all new lung cancer diagnoses, but in contrast to non-small-cell lung cancer, the implementation of targeted treatments in small-cell lung cancer has been limited, with little improvement in the clinical outcome in the last several decades. Exploring new pathways for targeted therapy, we have observed that extra-copies of the tRNA modifier TRIT1, involved in the translation of selenoproteins, confers sensitivity to arsenic trioxide in small-cell lung cancer. This finding could open a new therapeutic niche for a tumor type with such a dismal clinical course. The alteration of RNA modification patterns is emerging as a co…

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…

Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic…

2014

Background: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. Methods: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. Results: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients…

The Synthetic Cannabinoid WIN 55,212-2 Sensitizes Hepatocellular Carcinoma Cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-I…

2010

In this article, we demonstrate that the synthetic cannabinoid R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)-(1-naphthalenyl) methanone mesylate (WIN 55,212-2) sensitizes human hepatocellular carcinoma (HCC) cells to apoptosis mediated by tumor necrosis-related apoptosis inducing ligand (TRAIL). The apoptotic mechanism induced by treatment with WIN/TRAIL combination involved the loss of the mitochondrial transmembrane potential and led to the activation of caspases. In HCC cells, WIN treatment induced the up-regulation of TRAIL death receptor DR5, an effect that seemed to be related to the increase in the level of p8 and CHOP, two factors implicat…

Inducing Cold-Sensitivity in the Frigophilic Fly Drosophila montana by RNAi.

2016

Cold acclimation is a critical physiological adaptation for coping with seasonal cold. By increasing their cold tolerance individuals can remain active for longer at the onset of winter and can recover more quickly from a cold shock. In insects, despite many physiological studies, little is known about the genetic basis of cold acclimation. Recently, transcriptomic analyses in Drosophila virilis and D. montana revealed candidate genes for cold acclimation by identifying genes upregulated during exposure to cold. Here, we test the role of myo-inositol-1-phosphate synthase (Inos), in cold tolerance in D. montana using an RNAi approach. D. montana has a circumpolar distribution and overwinters…

Tyramide Signal Amplification for Immunoelectron Microscopy

2021

Demonstration of an efficient pumping scheme for a 7.36-nm Ni-like samarium soft x-ray laser

2010

The demonstration of a 7.36 nm Ni-like Sm soft x-ray laser pumped by 36 J of a Nd:glass chirped pulse amplification laser is presented. Double-pulse single-beam non-normal incidence pumping was applied for the efficient soft x-ray laser generation. Here the applied technique included a new single optic focusing geometry for large beam diameters, a single-pass grating compressor traveling-wave tuning capability and an optimized high energy laser double-pulse. This scheme has the potential for even shorter wavelength soft x-ray laser pumping.

<title>New PW stretcher-compressor design for PHELIX laser</title>

2005

With PHELIX (Petawatt High Energy Laser for heavy Ion EXperiments) a high energy/ultra-high intensity laser system is currently under construction at the GSI (Gesellschaft fur SchwerIonenforschung, Germany). In combination with the high current high energy ion accelerator facility this will provide worldwide unique experimental opportunities in the field of dense plasma physics and inertial fusion research. In the long pulse mode the laser system will provide laser pulses of up to 5 kJ in 1-10 ns pulses. In the high intensity mode pulse powers in excess of 1 PW will be achieved. For this the well known technique of chirped pulse amplification (CPA) will be implemented. A new CPA stretcher-c…