As these compounds were designed to provide PET ligands with high

As these compounds were designed to provide PET ligands with high metabolic stability, they are now radiolabeled with fluorine-18 and investigated in vivo.

Methods: BFR precursors were synthesized and reacted with fluorine-18 in dry MeCN in the presence of 2,2,2-kryptofix and K2CO3. In rats, biodistribution and PET studies were performed using [F-18]5a, [F-18]5b and [F-18]5c. The binding specificity was determined by administration of non-labeled WAY-100635 prior to the radiolabeled ligands.

Results: [F-18]5 ligands were synthesized in overall radiochemical yields of 24%-45%, respectively with a radiochemical purity of >98%.

Relatively good hippocampus to cerebellum ratios of 5.55, 4.79 and 5.45, respectively were reached at 45 min pi. However, PET studies indicated defluorination of the radioligands by showing high accumulation of radioactivity in the bones in the order of [F-18]5a approximate to[F-18]5b>[F-18]5c.

Conclusion: Also in vivo, the radioligands bind preferentially to the 5-HT1A receptor. Unfortunately, no metabolic stability with regard to defluorination was observed in rats. (c) 2012 Elsevier Inc. All rights reserved.”
“Objective: Invasive lung tumors are associated with intercellular adhesion Selleck Nec-1s molecule-1 (ICAM-1) expression. Secretory phospholipase A(2) (sPLA(2)) enzymes produce inflammatory mediators that stimulate ICAM-1 expression,

and upregulation of PLA(2) activity can enhance metastasis. We hypothesize a link between sPLA(2) activity, ICAM-1 expression, and tumor cell invasion. We propose that inhibition of sPLA(2) modulates ICAM-1

expression in cancer cells and attenuates their invasiveness.

Methods: Human lung adenocarcinoma cells (A549) were treated with an ICAM-1 blocking antibody and assayed for invasion. Lung cancer cells (A549 and H358) were then treated with an sPLA(2) inhibitor and evaluated by immunoblotting for ICAM-1 expression. Next cells (A549) treated with sPLA(2) inhibitor were assayed for invasion. Finally, sPLA(2) messenger RNA and protein expression were evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence microscopy, respectively. Statistical analysis was performed by the Student t test or analysis of variance, as appropriate.

Results: Antibody blockade of Carfilzomib datasheet ICAM-1 decreased lung cancer cell invasion. sPLA(2) inhibition significantly reduced ICAM-1 expression and invasion. sPLA(2) inhibition also significantly decreased sPLA(2) mRNA expression and immunofluorescent staining of sPLA(2).

Conclusions: sPLA(2) plays a significant role in mediating the inflammatory signals that induce ICAM-1 expression in lung cancer cells. Inhibition of the enzyme can significantly decrease ICAM-1 expression and subsequent cancer cell invasion. This lays the groundwork for further investigation into the cellular mechanisms of sPLA(2) and its role in lung cancer.

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