Longitudinal Imaging Studies of Tumor Microenvironment in Mice Treated with the mTOR Inhibitor Rapamycin

Rapamycin is an allosteric inhibitor of mammalian target of rapamycin, and inhibits tumor growth and angiogenesis. Recent studies suggested a possibility that rapamycin renormalizes aberrant tumor vasculature and improves tumor oxygenation. The longitudinal effects of rapamycin on angiogenesis and tumor oxygenation were evaluated in murine squamous cell carcinoma (SCCVII) by electron paramagnetic resonance imaging (EPRI) and magnetic resonance imaging (MRI) to identify an optimal time after rapamycin treatment for enhanced tumor radioresponse. Rapamycin treatment was initiated on SCCVII solid tumors 8 days after implantation (500–750 mm³) and measurements of tumor pO₂ and blood volume were conducted from day 8 to 14 by EPRI/MRI. Microvessel density was evaluated over the same time period by immunohistochemical analysis. Tumor blood volume as measured by MRI significantly decreased 2 days after rapamycin treatment. Tumor pO₂ levels modestly but significantly increased 2 days after rapamycin treatment; whereas, it decreased in non-treated control tumors. Furthermore, the fraction of hypoxic area (pixels with pO₂<10 mm Hg) in the tumor region decreased 2 days after rapamycin treatments. Immunohistochemical analysis of tumor microvessel density and pericyte coverage revealed that microvessel density decreased 2 days after rapamycin treatment, but pericyte coverage did not change, similar to what was seen with anti-angiogenic agents such as sunitinib which cause vascular renormalization. Collectively, EPRI/MRI co-imaging can provide non-invasive evidence of rapamycin-induced vascular renormalization and resultant transient increase in tumor oxygenation. Improved oxygenation by rapamycin treatment provides a temporal window for anti-cancer therapies to realize enhanced response to radiotherapy.     

Protein biomarkers in a mouse model of extremes in trait anxiety

Brain proteome analysis of mice selectively bred for either high or low anxiety-related behavior revealed quantitative and qualitative protein expression differences. The enzyme glyoxalase-I was consistently expressed to a higher extent in low anxiety as compared with high anxiety mice in several brain areas. The same phenotype-dependent difference was also found in red blood cells with normal and cross-mated animals showing intermediate expression profiles of glyoxalase-I. Another protein that showed a different mobility during two-dimensional gel electrophoresis was identified as enolase phosphatase. The presence of both protein markers in red or white blood cells, respectively, creates the opportunity to screen for their expression in clinical blood specimens from patients suffering from anxiety.     

Methane and Carbon Dioxide Flux Heterogeneity Mediated by Termite Mounds in Moist Tropical Forest Soils of Himalayan Foothills,India

Ecosystems - Termites are dominant soil macro-fauna in tropical forests, yet remain an uncertain component of the carbon budget in many regions. We investigated CH4 and CO2 flux patterns from...     

Respiratory gas exchanges of termites from the Sabah (Borneo) assemblage

Abstract.Oxygen uptake and carbon dioxide release at 28°C were determined in worker castes of twenty-six species of forest termites from the Danum Valley Conservation Area, south-east Sabah, by Warburg manometry. Metabolic rate varied inversely with body weight in a suite of soil-, wood/soil- and wood-feeding species, giving a slope (in a log–log plot) of – 0.63. However, a number of large species, actively foraging forms such as Macrotermes malaccensis, M. gilvus, Havilanditermes atripennis and Hospitalitermes hospitalis, but also the wood-feeding Schedorhinotermes sarawakensis, showed an oxygen consumption greater than expected for their body weight. Rates of methane emission were above 0.100 μmol g^–1 h^–1 in seventeen species, with very high fluxes in two wood/soil-feeders, Termes borneensis (0.546 ± 0.163 μmol g^–1 h^–1) and Prohamitermes mirabilis (0.303 ± 0.123 μmol g^–1 h^–1). Of the fifteen remaining species, seven were soil-feeders, five were wood-feeders, two were wood/litter-feeders and a single species fed on lichen and moss. Low or negligible CH₄ emissions (< 0.100 μmol g^–1 h^–1) were observed in three other species, all wood-feeders. An apparent respiratory quotient (RQ_app) was calculated using xCO₂ and xO₂ (corrected for methane emission, but not hydrogen). Mean RQ_app was at or above 1.00 in eleven species and between 0.95 and 1.00 in a further six species, the two sets of species together representing all trophic groups, including lichen-feeders. This is argued to be consistent with carbohydrate being the principal substrate supporting respiration.