Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET A receptor antagonism

Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET A and ET B, on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 ± 1.4, 4.5 ± 1.5, vs. 2.75 ± 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET A antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET A receptors. ET A antagonists are indicated as potential anti-cancer agents. © 2001 Cancer Research Campaign http://www.bjcancer.co

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In a core off Pakistan, we obtained 38 14C analyses by accelerator mass spectrometry (AMS) from a 4.4-m-thick, expanded, annually-laminated Last Glacial Maximum (LGM) section, bracketed by bioturbated intervals ascribed to the Heinrich-1 (H1) and Heinrich-2 (H2) equivalent events (52 14C analyses between 24-15 kyr BP). A floating varve age scale, anchored to the oxygen isotope record of the layer-counted GISP2 ice core at the H2/LGM boundary, results in an annually dated record for the LGM from 23,450-17,900 cal BP. The floating varve scale of the LGM provides us with a tentative calibration of local marine AMS 14C age dates to calendar years.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Time-Dependent Factors Inherent in the Age Equation for Determining Residence Times of Groundwater Using 14

From the 18th International Radiocarbon Conference held in Wellington, New Zealand, September 1-5, 2003.The radiocarbon concentration of dissolved inorganic carbon in groundwater is most logically and completely represented as the product of 5 time-variable factors; these are mutually independent, and all must be considered and evaluated to determine a groundwater residence time. In the case of one factor, the 14C/(12C+13C) ratio of atmospheric CO2, its time variability can be side-stepped by assuming it to be constant at the pre-bomb 1950 value, and assigning an apparent half-life in the radioactive decay term. Apparent half-lives are calculated here for 5 separate periods extending back to 24,000 BP, working from the INTCAL98 atmospheric calibration. This approach can be extended further back in time when the necessary atmospheric calibrations are updated with greater certainty. The procedure is applied to the recently-explored Wairau Deep Aquifer, underlying central areas of the coastal Wairau Plain, Marlborough. The evolution of dissolved inorganic carbon concentration for this river-recharged groundwater is apparent from distinct trends in 13C, and is confirmed by hydrochemical modelling. Extension to 14C concentrations yields minimum/maximum limits for groundwater residence times to 3 wells. In all 3 cases, the maximum is uncertain due to present uncertainty of the apparent half-life applicable before 24,000 BP. Residence times for the 2 wells closest to the recharge area are at least 17,400 yr, while that for a well further down the aquifer is at least 38,500 yr. Recharge, therefore, occurred during the Otiran glaciation, while the present-day near-surface fluvioglacial deposits of the Wairau Plain were accumulating. Drawdown-recovery records over 3 yr indicate a permeable connection to compensating recharge, enabling limited exploitation for vineyard irrigation.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Friction of melting ice

The friction of pure ice against various materuals was studied at the melting point by pulling plates of the materials of known roughness under a melting ice sample, which was loaded from above, and by maintaining a surrounding air temperature of +2\ub0C (\ub11\ub0C). Speed was varied over a wide range from 0.05 to 400 mm s^-1. Results for an aluminium sheet of roughness R_a = 0.84 \ub5m, showed a maximum in friction coefficient of 0.04 at a speed of 16 mm s^-1. Below this speed the friction coefficient fropped to 0.002 at 0.2 mm s^-1 and results from different ice samples were very reproducible. Above 16 mm s^-1, the friction coefficient initially dropped to about 0.002 at 100 mm s^-1 and then increased again to 0.037 at 400 mm s^-1. Results at speeds above 16 mm s^-1 were much less reproducible than those at lower speeds. Results are given also for the friction of ice on Formica, acrylic, and copper plates. The amount of meltwater produced during a test was measured by weighing an absorbent tissue before and after mopping-up the meltwater. The amount of meltwater was significantly more for aluminium than for Formica or acrylic, showing that the thermal conductivity of the slider was controlling the amount of meltwater. The amount was also a string function of velocity.Peer reviewed: YesNRC publication: Ye