692 research outputs found
Receptor tyrosine kinase and p16/CDKN2 expression in a case of tripe palms associated with non-small-cell lung cancer
Background: Tripe palms is a descriptive term for a cutaneous paraneoplastic keratoderma. Tripe palms are frequently associated with gastric and pulmonary carcinoma. The pathogenetic mechanism remains unknown. Objective: To determine the influence of receptor tyrosine kinases, which are both expressed in pulmonary carcinomas and in human skin, we performed expression studies on epidermal growth factor receptor (EGFR), HER2, HERS in a skin sample of tripe palms obtained from a patient with non-small-cell lung cancer with lymph node involvement. Two months after diagnosis, the patient had developed palmoplantar `tripe palms'. Additionally, the expression of SRC, c-myc and p16/CDKN2 were studied. Method: Conventional reverse-transcription polymerase chain reaction was performed on a tissue sample of tripe palms. Results: Weak expression of HER2 and of p16/CDKN2 was found. EGFR, HERS, c-myc and SRC were not expressed. Conclusion: Receptor tyrosine kinases of subclass I, the tyrosine kinase SRC and the oncogene c-myc play no major role in the pathogenesis of this case of tripe palms. Copyright (C) 2000 S. Karger AG. Basel
Single-Bottleneck Approximation for Driven Lattice Gases with Disorder and Open Boundary Conditions
We investigate the effects of disorder on driven lattice gases with open
boundaries using the totally asymmetric simple exclusion process as a
paradigmatic example. Disorder is realized by randomly distributed defect sites
with reduced hopping rate. In contrast to equilibrium, even macroscopic
quantities in disordered non-equilibrium systems depend sensitively on the
defect sample. We study the current as function of the entry and exit rates and
the realization of disorder and find that it is, in leading order, determined
by the longest stretch of consecutive defect sites (single-bottleneck
approximation, SBA). Using results from extreme value statistics the SBA allows
to study ensembles with fixed defect density which gives accurate results, e.g.
for the expectation value of the current. Corrections to SBA come from
effective interactions of bottlenecks close to the longest one. Defects close
to the boundaries can be described by effective boundary rates and lead to
shifts of the phase transitions. Finally it is shown that the SBA also works
for more complex models. As an example we discuss a model with internal states
that has been proposed to describe transport of the kinesin KIF1A.Comment: submitted to J. Stat. Mec
Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases
Amplification and overexpression of the c-myc gene have been associated with neoplastic transformation in a plethora of malignant tumours. We applied interphase fluorescence in situ hybridization (FISH) with a locus-specific probe for the c-myc gene (8q24) in combination with a corresponding chromosome 8 α-satellite probe to evaluate genetic alterations in 8 primary melanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spreads of 7 melanoma cell lines a whole chromosome 8 paint probe was used. We investigated the functionality of the c-myc gene by detecting c-myc RNA expression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals relative to the centromere of chromosome 8 copy number. None of the nevi, safety margins or normal skin samples demonstrated this gain. In 2/7 melanoma cell lines (C32 and WM 266–4) isochromosome 8q formation with a relative gain of c-myc copies and a loss of 8p was observed. The highest c-myc gene expression compared to GAPDH was found in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%) expressed the c-myc gene on a lower level. 72.7% of the patients with c-myc extra copies had visceral melanoma metastases (UICC IV), patients without c-myc gain in 35.0% only. The collective with additional c-myc copies also expressed the gene on a significantly higher level. These results indicate that a c-myc gain in relation to the centromere 8 copy number might be associated with advanced cutaneous melanoma. © 2001 Cancer Research Campaign http://www.bjcancer.co
Suitability versus fidelity for rating single-photon guns
The creation of specified quantum states is important for most, if not all,
applications in quantum computation and communication. The quality of the state
preparation is therefore an essential ingredient in any assessment of a
quantum-state gun. We show that the fidelity, under the standard definitions is
not sufficient to assess quantum sources, and we propose a new measure of
suitability that necessarily depends on the application for the source. We
consider the performance of single-photon guns in the context of quantum key
distribution (QKD) and linear optical quantum computation. Single-photon
sources for QKD need radically different properties than sources for quantum
computing. Furthermore, the suitability for single-photon guns is discussed
explicitly in terms of experimentally accessible criteria.Comment: 4 pages, 2 figures Revised per referee suggestion
Mutational pathway determines whether drug gradients accelerate evolution of drug-resistant cells
Drug gradients are believed to play an important role in the evolution of
bacteria resistant to antibiotics and tumors resistant to anti-cancer drugs. We
use a statistical physics model to study the evolution of a population of
malignant cells exposed to drug gradients, where drug resistance emerges via a
mutational pathway involving multiple mutations. We show that a non-uniform
drug distribution has the potential to accelerate the emergence of resistance
when the mutational pathway involves a long sequence of mutants with increasing
resistance, but if the pathway is short or crosses a fitness valley, the
evolution of resistance may actually be slowed down by drug gradients. These
predictions can be verified experimentally, and may help to improve strategies
for combatting the emergence of resistance.Comment: 6 pages, 3 figures, final version before acceptance to Phys. Rev.
Letters. P.G and B.W contributed equally to this wor
Chromosomes are predominantly located randomly with respect to each other in interphase human cells
To test quantitatively whether there are systematic chromosome–chromosome associations within human interphase nuclei, interchanges between all possible heterologous pairs of chromosomes were measured with 24-color whole-chromosome painting (multiplex FISH), after damage to interphase lymphocytes by sparsely ionizing radiation in vitro. An excess of interchanges for a specific chromosome pair would indicate spatial proximity between the chromosomes comprising that pair. The experimental design was such that quite small deviations from randomness (extra pairwise interchanges within a group of chromosomes) would be detectable. The only statistically significant chromosome cluster was a group of five chromosomes previously observed to be preferentially located near the center of the nucleus. However, quantitatively, the overall deviation from randomness within the whole genome was small. Thus, whereas some chromosome–chromosome associations are clearly present, at the whole-chromosomal level, the predominant overall pattern appears to be spatially random
Structure of the silicon vacancy in 6H-SiC after annealing identified as the carbon vacancy–carbon antisite pair
We investigated radiation-induced defects in neutron-irradiated and subsequently annealed 6H-silicon carbide (SiC) with electron paramagnetic resonance (EPR), the magnetic circular dichroism of the absorption (MCDA), and MCDA-detected EPR (MCDA-EPR). In samples annealed beyond the annealing temperature of the isolated silicon vacancy we observed photoinduced EPR spectra of spin S=1 centers that occur in orientations expected for nearest neighbor pair defects. EPR spectra of the defect on the three inequivalent lattice sites were resolved and attributed to optical transitions between photon energies of 999 and 1075 meV by MCDA-EPR. The resolved hyperfine structure indicates the presence of one single carbon nucleus and several silicon ligand nuclei. These experimental findings are interpreted with help of total energy and spin density data obtained from the standard local-spin density approximation of the density-functional theory, using relaxed defect geometries obtained from the self-consistent charge density-functional theory based tight binding scheme. We have checked several defect models of which only the photoexcited spin triplet state of the carbon antisite–carbon vacancy pair (CSi-VC) in the doubly positive charge state can explain all experimental findings. We propose that the (CSi-VC) defect is formed from the isolated silicon vacancy as an annealing product by the movement of a carbon neighbor into the vacancy
Modeling genomic diversity and tumor dependency in malignant melanoma
The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors
- …