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 https://www.selleckchem.com/products/isrib-trans-isomer.html 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.