Recombinant human erythropoietin α modulates the effects of radiotherapy on colorectal cancer microvessels

Recent data suggest that recombinant human erythropoietin (rhEPO) modulates tumour growth and therapy response. The purpose of the present study was to examine the modulation of radiotherapy (RT) effects on tumour microvessels by rhEPO in a rat colorectal cancer model. Before and after 5 × 5 Gy of RT, dynamic contrast-enhanced -magnetic resonance imaging was performed and endothelial permeability surface product (PS), plasma flow (F), and blood volume (V) were modelled. Imaging was combined with pO2 measurements, analysis of microvessel density, microvessel diameter, microvessel fractal dimension, and expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 α (HIF-1α), Bax, and Bcl-2. We found that RT significantly reduced PS and V in control rats, but not in rhEPO-treated rats, whereas F was unaffected by RT. Oxygenation was significantly better in rhEPO-treated animals, and RT induced a heterogeneous reoxygenation in both groups. Microvessel diameter was significantly larger in rhEPO animals, whereas VEGF expression was significantly lower in the rhEPO group. No differences were observed in HIF-1α, Bax, or Bcl-2 expression. We conclude that rhEPO results in spatially heterogeneous modulation of RT effects on tumour microvessels. Direct effects of rhEPO on neoplastic endothelium are likely to explain these findings in addition to indirect effects induced by increased oxygenation

Correction of anaemia through the use of darbepoetin alfa improves chemotherapeutic outcome in a murine model of Lewis lung carcinoma

Darbepoetin alfa (Aranesp®, Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours contain regions of hypoxia due to poor vascular supply and cellular compaction. Although hypoxic stress usually results in cell death, hypoxia-resistant tumour cells are genetically unstable and often acquire a drug-resistant phenotype. Increasing tumour oxygenation and perfusion during treatment could have the doubly beneficial outcome of reducing the fraction of treatment-resistant cells, while increasing drug delivery to previously hypoxic tissue. In this study, we examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery in an in vivo model of Lewis lung carcinoma, shown here to express the Epo receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing 10 days before chemotherapy, resulted in a significant reduction in tumour volume compared to chemotherapy alone. This was mediated by the prevention of anaemia, a reduction in tumour hypoxia and a concomitant increase in drug delivery. Darbepoetin alfa treatment alone did not modulate the growth of the EpoR-expressing tumour cells. This study identifies an important role for darbepoetin alfa in increasing the therapeutic index of chemotherapy

Leisure pilot license proposed for Europe : Do you want such pilots crossing your flight path?

Dit artikel bevat een op uitnodiging geschreven kritisch commentaar op de door de European Aviation Safety Agency voorgestelde regelgeving m.b.t. een “Leisure Pilot License”

A comparative study of arsenic accumulation in agricultural fields

A study has been carried out to determine the fate of Arsenic (As) supplied to agriculture fields (through contaminated irrigation water), and the relationship between As accumulation in agriculture soils and the crop pattern. A paddy and a wheat cultivating agriculture field irrigated by contaminated water having As concentration of 137 μg/L and 67.3 μg/L were selected. Results clearly indicate that in comparison to wheat field though higher quality of contaminated water was used in paddy field but still paddy field soils show lesser As accumulation. Such an accumulation indicate the existence of an effective As removal mechanism in paddy soils. Absence of any such mechanism in wheat fields is responsible for build-up of As in wheat soils. Different harvesting methods applied in paddy and wheat cultivation are responsible for different accumulation of As in agriculture soils

Calcretes from a Late Quaternary interfluve in the Ganga Plains, India: carbonate types and isotopic systems in a monsoonal setting

Calcretes are abundant in Late Quaternary channel and floodplain strata of the southern Ganga plains. In a key section at Kalpi, pedogenic carbonates (nodules, rhizoconcretions, and powdery carbonate) are present within aggradational floodplain deposits, where they correspond to relatively high monsoonal precipitation and river discharge. In contrast, groundwater carbonate has cemented degradational surfaces (discontinuities), which correspond with periods of relatively low precipitation. Mixed groundwater and pedogenic calcretes are present in the deposits of small interfluve channels, and reworked nodules line degradational surfaces and locally fill channels. Most carbonates show alpha fabrics that include floating textures, shrinkage crack fills, and grain coatings. The predominance of alpha fabrics is unexpected, but is characteristic of calcretes across dryland and seasonal parts of northern India, where soil formation led to only weakly developed or poorly preserved beta fabrics. Interpretation of δ13C and δ18O values of bulk and microdrilled calcrete samples suggests relatively little variation in precipitation and vegetation types through the sampled interval at Kalpi. Floodplain deposits were vegetated with a mixture of C4 and C3 plants (predominantly C4), with a higher proportion of C3 plants associated with channel deposits. This apparent lack of variation is surprising because the sampled interval represents at least 60,000 years of Marine Isotope Stages 3-5, during which climate models suggest that Asia experienced radical fluctuations in monsoon intensity and precipitation. Some of the apparent lack of variation may be explained by preferential preservation of aggradational strata that represent relatively active monsoonal periods, as well as by the mixing of drier floodplain (C4) and riparian (C3) vegetation. However, local departures from the regionally based climate model cannot be ruled out. A modest upsection increase in C4 plants may represent increased aridity and lower atmospheric CO2. Isotopic analysis of organic matter from floodplain pedogenic nodules suggests a higher C3 plant contribution than carbonate-based data would suggest. The preserved organic matter may reflect the annual average biomass in the soil, whereas carbonate formation may have taken place mainly during the drier season when respiration of C4 plants was more important. In interfluve settings such as Kalpi, seasonality may strongly affect the C3-C4 system, with preferential preservation of only part of the biomass