Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

Studies have suggested that an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to the malignant phenotype of gliomas. In this study, we have undertaken a detailed analysis of expression of the TIMP family in normal human brain and malignant gliomas at both the mRNA and protein level. Reverse transcription-PCR (RT-PCR) analyses of total RNA from surgical tumour specimens revealed unique expression patterns for the 4 members of the TIMP family, with TIMP-1 and -4 showing positive and negative correlations, respectively, with glioma malignancy. By RT-PCR, TIMP-2 and TIMP-3 expression did not change with tumour grade. In situ hybridization localized TIMP-1 to glial tumour cells and also to the surrounding tumour vasculature. TIMP-4 transcripts were predominantly localized to tumour cells, though minor expression was found in vessels. Recombinant TIMP-4 reduced invasion of U251 glioma cells through Matrigel, and U87 clones overexpressing TIMP-4 showed reduced invasive capacity in vitro. TIMP-4, but not TIMP-1, blocked Membrane Type-1-MMP-mediated progelatinase-A (MMP-2) activation in human umbilical vein endothelial cells. The differential expression and localization of individual TIMPs may contribute to the pathophysiology of human malignant gliomas, particularly with regard to tumour vascularization. © 2001 Cancer Research Campaign http://www.bjcancer.co

Diffuse glioma growth: a guerilla war

In contrast to almost all other brain tumors, diffuse gliomas infiltrate extensively in the neuropil. This growth pattern is a major factor in therapeutic failure. Diffuse infiltrative glioma cells show some similarities with guerilla warriors. Histopathologically, the tumor cells tend to invade individually or in small groups in between the dense network of neuronal and glial cell processes. Meanwhile, in large areas of diffuse gliomas the tumor cells abuse pre-existent “supply lines” for oxygen and nutrients rather than constructing their own. Radiological visualization of the invasive front of diffuse gliomas is difficult. Although the knowledge about migration of (tumor)cells is rapidly increasing, the exact molecular mechanisms underlying infiltration of glioma cells in the neuropil have not yet been elucidated. As the efficacy of conventional methods to fight diffuse infiltrative glioma cells is limited, a more targeted (“search & destroy”) tactic may be needed for these tumors. Hopefully, the study of original human glioma tissue and of genotypically and phenotypically relevant glioma models will soon provide information about the Achilles heel of diffuse infiltrative glioma cells that can be used for more effective therapeutic strategies

Interferometric measurement of ionization in a grassfire

Grassfire plumes are weakly ionized gas. The ionization in the fire plume is due to thermal and chemi-ionization of incumbent species, which may include graphitic carbon, alkalis and thermally excited radicals, e.g., methyl. The presence of alkalis (e.g., potassium and sodium) in the fires makes thermal ionization a predominant electron producing mechanism in the combustion zone. Alkalis have low dissociation and ionization potentials and therefore require little energy to thermally decompose and give electrons. Assuming a Maxwellian velocity distribution of flame particles and electron-neutral collision frequency much higher than plasma frequency, the propagation of radio waves through a grassfire is predicted to have attenuation and phase shift. Radio wave propagation measurements were performed in a moderate intensity (554 kW m^−1) controlled grassfire at 30- and 151-MHz frequencies on a 44 m path using a radio wave interferometer. The maximum temperature measured in the controlled burn was 1071 K and the observed fire depth was 0.9 m. The radio wave interferometer measured attenuation coefficients of 0.033 and 0.054 dB m^−1 for 30- and 151-MHz, respectively. At collision frequency of 1.0 × 10^11 s^−1, maximum electron density was determined to be 5.061 × 10^15 m^−3