Gene expression deregulation by <Emphasis Type="Italic">KRAS</Emphasis> G12D and G12V in a <Emphasis Type="Italic">BRAF</Emphasis> V600E context

Background  

KRAS and BRAF mutations appear of relevance in the genesis and progression of several solid tumor types but the co-occurrence and interaction of these mutations have not yet been fully elucidated. Using a microsatellite stable (MSS) colorectal cancer (CRC) cell line (Colo741) having mutated BRAF and KRAS ^WT , we also aimed to investigate the KRAS-BRAF interaction. Gene expression profiles for control KRAS ^WT , KRAS ^G12V and KRAS ^G12D transfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data.     

Methylation of O6-methylguanine DNA methyltransferase and loss of heterozygosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival.

PURPOSE: Recent data suggest that methylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase (MGMT), by increasing the chemosensitivity of glioblastoma multiforme, is significantly associated with improved prognosis. Results in contradiction with these findings, however, are present in the literature and the clinical and genetic context framing MGMT methylation is poorly characterized. EXPERIMENTAL DESIGN: To address these issues, we have investigated the MGMT methylation status, clinical and magnetic resonance imaging characteristics, and relevant genetic features (loss of heterozygosity on 17p and 19q, EGFR amplification, and p53 mutations) in a retrospective study on 86 patients affected by glioblastoma multiforme: 72 patients had a clinical history indicating de novo insurgence of the tumor and the remaining 14 were secondary glioblastoma multiforme. RESULTS: MGMT methylation was detected by methylation-specific PCR in 41 of 86 cases (47.7%; Meth+). Progression-free survival and overall survival were significantly longer in Meth+ than in Meth- patients [10 versus 7 months (P=0.003, log-rank test) and 18 versus 14 months (P=0.0003, log-rank test), respectively]. Mixed-nodular enhancement at magnetic resonance imaging was significantly more frequent in Meth+ and secondary glioblastoma multiforme and ring enhancement in Meth- and primary glioblastoma multiforme (P<0.005). MGMT methylation was more present in secondary glioblastoma multiforme (P=0.006) and associated with loss of heterozygosity on 17p and/or 19q (P=0.005). CONCLUSIONS: These observations suggest that MGMT methylation is part of a genetic signature of glioblastomas that developed from lower-grade gliomas.     

Acute upper airway obstruction caused by Stenotrophomonas maltophilia soft tissue infection

A previously healthy 71-y-old male developed acute upper airway obstruction caused by a Stenotrophomonas maltophilia infection of the mucocutaneous and soft tissue of the neck. Ventilator support was provided via a small-calibre endotracheal tube. Stenotrophomonas was susceptible only to levofloxacin and cotrimoxazole. Antibiotic therapy rapidly improved the soft tissue oedema, allowing extubation and discharge from the intensive care unit.     

Plasminogen activator inhibitor 1 and miscarriage after metformin treatment and laparoscopic ovarian drilling in patients with polycystic ovary syndrome

In women with polycystic ovary syndrome, metformin administration, not laparoscopic ovarian drilling, reduces plasminogen activator inhibitor 1 (PAI-1) activity. The lack of a decrease in PAI-1 activity is related to a high risk for miscarriage.     

Increased plasma concentrations of palmitoylethanolamide, an endogenous fatty acid amide, affect oxidative damage of human low-density lipoproteins: an in vitro study

Fatty acid ethanolamides (NAEs) are naturally occurring hydrophobic molecules usually present in a very small amount in many mammalian tissues and cells. Moreover, these compounds have been isolated in mammalian biological fluids, such as blood. Palmitoylethanolamide (C16:0) (PEA) is a fully saturated NAE, which presents some possible pharmaceutical activities, such as anti-inflammatory and antinociceptive effects. PEA is physiologically present in the mammalian blood at concentrations ranging from 9.4 to 16.7 pmol/ml. Since increasing evidence indicates that oxidative modification of low-density lipoproteins (LDL) is an important determinant in atherogenesis, the aim of this study was to evaluate the effect of physiologically relevant concentrations of PEA on Cu2+-induced LDL oxidation (measured as conjugated dienes formation). Our experiments indicate both anti-oxidative and slightly pro-oxidative effects of PEA. The anti-oxidative effect is obtained at low PEA concentrations (0.01 and 0.1 microM), while the pro-oxidative effect is obtained at a higher PEA concentration (1 microM). Fluorescence and circular dichroism data indicate that the effect of PEA occurs mainly by affecting the conformational features of ApoB-100.