Presently, there is no effective treatment for glioblastoma, the most malignant and common brain tumor. Growth factors are potential targets for therapeutic strategies because they are essential for tumor growth and progression. Peptidylglycine ␣-amidating monooxygenase is the enzyme producing ␣-amidated bioactive peptides from their inactive glycine-extended precursors. The high expression of peptidylglycine ␣-amidating monooxygenase mRNA in glioblastoma and glioma cell lines points to the involvement of ␣-amidated peptides in tumorigenic growth processes in the brain. After screening of amidated peptides, it was found that human glioblastoma cell lines express high levels of adrenomedullin (AM) mRNA, and that immunoreactive AM is released into the culture medium. AM is a multifunctional regulatory peptide with mitogenic and angiogenic capabilities among others. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis showed that AM mRNA was correlated to the tumor type and grade, with high expression in all glioblastomas analyzed, whereas a low expression was found in anaplastic astrocytomas and barely detectable levels in low-grade astrocytomas and oligodendrogliomas. In the present study we also demonstrate the presence of mRNA encoding the putative AM receptors, calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CRLR/RAMP2; CRLR/RAMP3) in both glioma tissues and glioblastoma cell lines and further show that exogenously added AM can stimulate the growth of these glioblastoma cells in vitro. These findings suggest that AM may function as an autocrine growth factor for glioblastoma cells. One way to test the autocrine hypothesis is to interrupt the function of the endogenously produced AM. Herein, we demonstrate that a polyclonal antibody specific to AM, blocks the binding of the hormone to its cellular receptors and decreases by 33% (P < 0.001) the growth of U87 glioblastoma cells in vitro. Malignant glioblastomas are highly aggressive tumors with a median patient survival time of 9 to 14 months.

Since the few data exploring a possible association between Epstein–Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a 35 S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade. © 2001 Cancer Research Campaign http://www. bjcancer.com

Methane and krypton adsorption measured on single-walled nanotubes at 78.7 and 77.3 K, respectively, give rise to stepwise isotherms, representative of the adsorption on two types of comparatively uniform patches during the first stages of the adsorbate condensation. The values of the methane isosteric heat of adsorption on these two fractions of quasi-uniform surface, determined from the dependence of the equilibrium pressure on temperature between 78 and 110 K, are in very good agreement with those measured at 77.3 K by means of isothermal microcalorimetry in quasi-equilibrium. Their respective mean values (18.3 ± 1 and 11.2 ± 0.5 kJ mol-1) enclose that of methane adsorption on graphite in the monolayer range (14.9 kJ mol-1). A phase transition occurring in the adsorbed film on the less attractive quasi-uniform part of the surface can be predicted from volumetric measurements.

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Transforming growth factor-beta (TGFb)1 is thought to be implicated in breast cancer progression. However, data about the influence of TGFb1 on breast cancer development are conflicting. To clarify the clinical relevance of TGFb1, TGFb1 protein level has been measured by enzyme-immoassay in 193 breast tumour samples. We found that 94.3% of patients expressed TGFb1 with a range of 0 -684 pg mg À1 protein.In the overall population, an increase of tumoral TGFb1 was observed in premenopausal patients when compared to postmenopausal subgroup (P ¼ 0.0006). When patients were subdivided according to nodal status, TGFb1 was correlated to type-1 plasminogen activator inhibitor in the node-negative subgroup (P ¼ 0.040). Multivariate analysis revealed that, after lymph node status (P ¼ 0.0002) and urokinase-type plasminogen activator (P ¼ 0.004), TGFb1 was an independent prognostic marker for DFS (P ¼ 0.005) in the overall population. In the node-negative population, TGFb1 was the prominent prognostic factor (P ¼ 0.010). In the same population, Kaplan -Meier curves demonstrated that high TGFb1 level was correlated with a shorter diseasefree survival (P ¼ 0.020). These data suggest that the measurement of tumoral TGFb1 protein level, especially for node-negative patients, might help to identify a high-risk population early in tumour progression.

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We report experimental studies of the adsorption characteristics and structure of both 36Ar and 40Ar on single-wall carbon nanotube bundles. The structural studies make use of the large difference in coherent neutron scattering cross section for the two Ar isotopes to explore the influence of the adsorbate on the nanotube lattice parameter. We observe no dilation of the nanotube lattice with 40Ar, and explain the apparent expansion of this lattice upon 36Ar adsorption by the location of the adsorbed Ar atoms on the outer bundle surface.

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