Invasive colorectal cancer is associated with poor prognosis requiring treatment with systemic chemotherapies usually including 5-fluorouracil. A consequence of prolonged treatment is the acquisition ...of resistance eventually resulting in the recurrence of highly metastatic cancer cells. To address the relationship between drug resistance and increased lymphatic metastatic potential, we used a 3D co-culture model of colon tumour cell spheroids of parent CCL227 cells and subclones with gradually increasing resistance against 5-fluorouracil. From each investigated cell line, homogeneous tumour spheroids were generated in the presence of methylcellulose yielding emboli of ∼700 µm diameter. When invasive, tumour spheroids disrupt the continuous lymphendothelial cell (LEC) layer and generate a 'circular chemorepellent-induced defect' (CCID), reminiscent of the entry gates through which tumour emboli intravasate lymphatic vasculature. Here we provide evidence that increasingly chemoresistant colon cancer spheroids were strongly associated with enhanced intravasative properties. In naïve CCL227 spheroids, miR-200 family members were released into exosomes thereby repressing the epithelial to mesenchymal transition-regulating transcription factors ZEB1 and SLUG in LEC. As a consequence of attenuated plasticity and migration of LEC, CCID formation was impaired. Loss of exosomal transferred miR-200c in resistant colon cells rendered LEC more susceptible to pro-migratory signals that were generated and directly transmitted by colon cancer spheroids. This observation indicates a common molecular axis in colon cancer and LEC where miR-200 family members act as regulators of ZEB proteins. The data support the notion that horizontal miR-200 signalling prevents the permeation of cells into adjacent epithelia and contributes to organ integrity.
Many cell lines derived from solid cancers can form spheroids, which recapitulate tumor cell clusters and are more representative of the in vivo situation than 2D cultures. During spheroid formation, ...a small proportion of a variety of different colon cancer cell lines did not integrate into the sphere and lost cell-cell adhesion properties. An enrichment protocol was developed to augment the proportion of these cells to 100% purity. The basis for the separation of spheroids from non-spheroid forming (NSF) cells is simple gravity-sedimentation. This protocol gives rise to sub-populations of colon cancer cells with stable loss of cell-cell adhesion. SW620 cells lacked E-cadherin, DLD-1 cells lost α-catenin and HCT116 cells lacked P-cadherin in the NSF state. Knockdown of these molecules in the corresponding spheroid-forming cells demonstrated that loss of the respective proteins were indeed responsible for the NSF phenotypes. Loss of the spheroid forming phenotype was associated with increased migration and invasion properties in all cell lines tested. Hence, we identified critical molecules involved in spheroid formation in different cancer cell lines. We present here a simple, powerful and broadly applicable method to generate new sublines of tumor cell lines to study loss of cell-cell adhesion in cancer progression.
Striking field-induced changes in the absorption near the Si L-edge of SiO2 exposed to a near-infrared laser field of several V/Å delivered by a few-cycle pulse are observed with sub-100 attosecond ...extreme ultraviolet pulses by means of attosecond transient absorption.
Photodissociation of ozone following absorption of biologically harmful solar ultraviolet radiation is the key mechanism for the life protecting properties of the atmospheric ozone layer. Even though ...ozone photolysis is described successfully by post-Hartree-Fock theory, it has evaded direct experimental access so far, due to the unavailability of intense ultrashort deep ultraviolet radiation sources. The rapidity of ozone photolysis with predicted values of a few tens of femtoseconds renders both ultrashort pump and probe pulses indispensable to capture this manifestation of ultrafast chemistry. Here, we present the observation of femtosecond timescale electronic and nuclear dynamics of ozone triggered by ∼10-fs, ∼2-µJ deep ultraviolet pulses and, in contrast to conventional attochemistry experiments, probed by extreme ultraviolet isolated pulses. An electronic wave packet is first created. We follow the splitting of the excited B-state related nuclear wave packet into a path leading to molecular fragmentation and an oscillating path, revolving around the Franck-Condon point with 22-fs wave-packet revival time. Full quantum-mechanical ab initio multiconfigurational time-dependent Hartree simulations support this interpretation.
We report a broadband mid-IR femtosecond OPO tunable across 2179-3732 nm, pumped by 20-fs pulses at 790 nm, generating idler pulses of 4.3 optical cycles (33 fs) at 2282 nm, with high stability and ...beam-quality.
Striking field-induced changes in the absorption near the Si L-edge of SiO sub(2) exposed to a near-infrared laser field of several V/A delivered by a few-cycle pulse are observed with sub-100 ...attosecond extreme ultraviolet pulses by means of attosecond transient absorption.
X-ray observations of 4U/MXB 1735 – 44 Lewin, W. H. G.; van Paradijs, J.; Cominsky, L. ...
Monthly notices of the Royal Astronomical Society,
11/1980, Letnik:
193, Številka:
1
Journal Article
Recenzirano
MXB 1735–44 was observed with the SAS-3 X-ray observatory on five occasions in 1977 and 1978. It was always ‘burst active’. Fifty-three bursts were observed in a total of about 20 days. The intervals ...between bursts were highly irregular, varying from ∼ 2 to more than 50 hr. In the framework of the thermonuclear flash model for X-ray bursts, the irregular burst behaviour of MXB 1735 – 44 (and of MXB 1837 + 05) may be related to its high intrinsic X-ray luminosity. We have looked for possible correlations between burst frequency and properties of the associated persistent source (flux and hardness of the persistent spectrum). No such correlations were found. There is probably a correlation between the size of the bursts and the burst intervals: the bursts tend to be smaller when they occur more frequently. The distributions of the burst sizes in terms of their integrated burst flux Eb and maximum burst flux Fmax both have standard deviations (normalized to the mean value) of ∼ 37 per cent. Taking the smallest and largest burst, the total range in both Eb and Fmax is about a factor of 7. However, the ratio Eb/Fmax is approximately constant. We also found that there is no statistically significant evidence for a variation in blackbody radii with burst size. No periodic pulsations were found in the persistent emission: for periods between 1.5 and ∼ 1000 s the 3 σ upper limit to the pulsed fraction is 2 per cent.
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