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.

Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics.

Objective: This study compared the potency of a somatostatin receptor (sstr)2 -sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule, BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing, enhanced affinities for sstr2, sstr5 and DAD2, BIM-23A758, BIM-23A760 and BIM-23A761, to suppress GH and prolactin (PRL) from 18 human GH adenomas that are partially responsive to octreotide or lanreotide. Materials and methods: The sstr2, sstr5 and DAD2 mRNA levels were determined by RT-PCR. The effect of drugs was tested in cell cultures at various concentrations. Results: In all tumors, the sstr2, sstr5 and DAD2 mRNA levels were coexpressed (mean levels^S.E.M. 0.4^0.1, 5.3^1.9 and 2.0^0.4 copy/copy b-glucuronidase). In 13 tumors, the maximal suppression of GH secretion produced by BIM-23A387 (30^3%) and BIM-23244 (28^3%) was greater than that produced by octreotide (23^3%). In six out of 13 tumors, BIM-23A758, BIM-23A760 and BIM-23A761 produced greater maximal suppression of GH secretion than octreotide (33^5, 38^2 and 41^2 vs 24^2%). Their EC 50 values were 10, 2 and 4 pmol/l. BIM-23A761 was more effective than BIM-23A387 in GH suppression (41^2 vs 32^4%). The new chimeric molecules produced maximal PRL suppression greater than octreotide (62^8 to 74^5 vs 46^11%). Conclusions: Novel dopamine-somatostatin chimeric molecules with differing, enhanced activity at sstr2, sstr5 and DAD2, consistently produced significatly greater suppression of GH and PRL than either octreotide or single-receptor-interacting ligands in tumors from patients classified as only partially responsive to octreotide therapy. The higher efficacy of the chimeric compounds was, at least partially, linked to their high affinity for sstr2 (IC 50 1-10 pmol/l). The other mechanisms by which such molecules produce an enhanced inhibition of GH remain to be elucidated.

Background. Brain abscess is commonly treated using empirically prescribed antibiotics. Thus, a comprehensive study of bacterial organisms associated with brain abscess is essential to define the best empirical treatment for this life-threatening condition. Methods. We prospectively compared cultures to single and multiple sequenced 16S ribosomal DNA polymerase chain reaction amplifications (by cloning and/or pyrosequencing) of cerebral abscesses in 20 patients from 2 hospitals in Marseilles, France, during the period January 2005 through December 2007. Results. The obtained cultures identified significantly fewer types of bacteria (22 strains) than did molecular testing (72 strains; P = .017, by analysis of variance test). We found that a patient could exhibit as many as 16 different bacterial species in a single abscess. The obtained cultures identified 14 different species already known to cause cerebral abscess. Single sequencing performed poorly, whereas multiple sequencing identified 49 species, of which 27 had not been previously reported in brain abscess investigations and 15 were completely unknown. Interestingly, we observed 2 patients who harbored Mycoplasma hominis (an emerging pathogen in this situation) and 3 patients who harbored Mycoplasma faucium, which, to our knowledge, has never been reported in literature. Conclusions. Molecular techniques dramatically increased the number of identified agents in cerebral abscesses. Mycoplasma species are common and should be detected in this situation. These findings led us to question the accuracy of the current empirical treatment of brain abscess.

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