Co-Targeting MAP Kinase and Pi3K-Akt-mTOR Pathways in Meningioma: Preclinical Study of Alpelisib and Trametinib.

Recurrent or high-grade meningiomas are an unmet medical need. Recently, we demonstrated that targeting mTOR by everolimus was relevant both in vitro and in humans. However, everolimus induces an AKT activation that may impact the anti-proliferative effect of the drug. Moreover, the MAP kinase pathway was shown to be involved in meningioma tumorigenesis. We therefore targeted both the Pi3k-AKT-mTOR and MAP kinase pathways by using combinations of the Pi3k inhibitor alpelisib and the MEK inhibitor trametinib. Our study was performed in vitro on the human meningioma cell lines and on a large series of primary cultures providing from 63 freshly operated meningiomas including 35 WHO grade 1, 23 grade 2, and five grade 3, half of which presented a NF2 genomic alteration. Alpelisib induced a higher inhibitory effect on cell viability and proliferation than everolimus in all cell lines and 32 randomly selected tumors no matter the genomic status, the histological subtype or grade. Trametinib also strongly inhibited cell proliferation and induced AKT activation. Combined treatment with alpelisib plus trametinib reversed the AKT activation induced by trametinib and induced an additive inhibitory effect irrespective of the cell lines or tumor features. Co-targeting pathways seems promising and may be considered particularly for aggressive meningioma.

Autochthonous liver cystic hydatid: Past or actual French shepherd's disease?

Autochthonous hydatidosis in France and western Europa are uncommon since the beginning of the 21st century. We report here an authentic indigenous cystic echinococcosis case in a French shepherd. The risk of remerging pathology should not be neglected and measures to interrupt parasite transmission are still relevant.

Fluorescence in situ hybridization microscopic detection of Bacilli Calmette Guérin mycobacteria in aortic lesions: A case report.

RATIONALE: To improve the diagnosis of life-threatening Bacilli Calmette Guérin (BCG) arterial aneurysm in patients treated by intravesical instillation of BCG vaccine as adjunctive therapy for non-muscular bladder carcinoma, is a life-threatening condition. Its diagnosis remains cumbersome. PATIENT CONCERNS: One patient with a history of intravesical BCG installation presented with aortic aneurysm with routine microscopic examination after Ziehl-Neelsen staining remaining negative. DIAGNOSES: We used fluorescence in situ hybridization (FISH) to target the Mycobacterium tuberculosis complex rpob gene in a fresh aortic specimen. FISH yielded fluorescent mycobacteria in aortic lesions; mycobacteria were further confirmed as Mycobacterium bovis BCG mycobacteria by polymerase chain reaction (PCR) sequencing. INTERVENTIONS: The patient benefited from an antituberculous treatment combining rifampicin, isoniazid, and ethambunol. OUTCOME: A 9-month follow-up indicated a favorable outcome. LESSONS: This case report teaches that FISH targeting the M tuberculosis complex rpoB gene should be incorporated in the laboratory investigation of aortic aneurysm in patients with a history of bladder carcinoma.

Bicyclo[4.4.0]decane oxygenated sesquiterpenes from Eryngium maritimum essential oil.

Investigation of the essential oil of the aerial parts of Eryngium maritimum L. from Corsica led to the isolation of one known sesquiterpene (1) and three new oxygenated sesquiterpenes with a muurolane or cadinane skeleton (2-4). Structure assignments of 4 ßH -muurol-9-en-15-al (1), 4 ßH -cadin-9-en-15-al (2), 4 ßH -muurol-9-en-15-ol (3) and 4 ßH -cadin-9-en-15-ol (4) were carried out by GC/MS (EI and CI) and comprehensive 1D and 2D NMR spectroscopy. Antibacterial activity of Eryngium maritimum L. oil and column chromatography fractions have been investigated for the first time. The oxygenated fraction, which contains the four sesquiterpenes, was efficient against Listeria monocytogenes and Echerichia coli.

Chemical compositions of the essential oils of the aerial parts of Chamaemelum mixtum (L.) Alloni.

The chemical compositions of the aerial parts essential oils of Chamaemelum mixtum (L.) Alloni from Corsica and Sardinia were investigated employing gas chromatography and gas chromatography-mass spectrometry (GC-MS). The structure of (Z)-heptadeca-9,16-dien-7-one, a natural compound not previously described, was elucidated by GC-MS (electron impact and chemical ionization) and one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy. The variation in C. mixtum essential oil was studied, and statistical analysis showed the clustering of oil samples into three groups according to the amount of oxygenated compounds; these groups correlated to the harvest area. The strong biological activity of the oxygenated fraction (minimum inhibitory concentration of <0.1 mg/mL) of the Corsican oil against Candida albicans , Citrobacter frendii , Enterococcus faecalis , Escherichia coli , Klebsiella pneumoniae , Listeria monocytogenes , and Staphyllococcus aureus can be attributed to the presence of irregular monoterpene alcohols and (Z)-heptadeca-9,16-dien-7-one.

Identification of chrysanthenyl esters from the essential oil of Anthemis maritima L. investigated by GC/RI, GC-MS (EI and CI) and 13C-NMR spectroscopy: chemical composition and variability.

INTRODUCTION: Anthemis maritima L. (Asteraceae) is a wild plant growing in Corsica and Sardinia. No previous studies of the chemical composition of A. maritima essential oil have been found. The oil contains two series of cis- and trans-chrysanthenyl esters for which the MS data are not present in available libraries and the 13C-NMR data are not reported in the literature. The determination of these compounds is a challenging problem since some of these esters are present in low concentrations and they exhibit very similar EI-MS. OBJECTIVE: To develop comprehensive strategies involving integrated techniques including CC, GC/RI, GC-MS (EI and CI), 1H- and 13C-NMR and hemi-synthesis for the identification of both series of chrysanthenyl esters in A. maritima oils. METHODOLOGY: Seventeen oil samples were prepared by hydrodistillation. A fine analysis of a pool of Corsican oils was conducted after repeated CC. A selected Sardinian oil was used as source of product for the hemi-synthesis of chrysanthenyl esters. The identification of these compounds was based on joint information from GC-MS (EI and CI), 13C-NMR and hemi-synthesis. RESULTS: Integrated analysis of Corsican and Sardinian oils allowed the identification of 124 components accounting for 83.3-91.6% of the total oil. With the aid of principal component analysis, oil samples could be divided in two groups. Among 16 chrysanthenyl esters identified, 12 were laboratory-synthesised and their 13C-NMR data are reported for the first time. CONCLUSIONS: The study illustrates the contribution of integrated techniques for the characterisation of unusual essential oils.