Search

Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients. [ABSTRACT FROM AUTHOR]

Various acidic anhydrides including cantharidin were converted into corresponding aminobenzylcantharidinimide 3a and analogous imides 3b∼k (at the ortho, meta, and para positions) with 35%∼87% yields by reacting with aminobenzylamines and triethylamine. The two methyl side chains of cantharidinimides 3ao, 3am, and 3ap, and related imides had more than two chiral centers; the lone pair of electrons of nitrogen displayed a different chemical shift and coupling constant in H-NMR spectra when the amino group of benzylamine was in the ortho position. These cantharidinimides had parent aniline, pyridine, and naphthalene plane structures, and the primary amine nucleophilicity and basicity might reflect the inductive electron's negative effect on chemical shifts. We prepared cantharidinimides by heating the reactants cantharidin 1a, aliphatic and aromatic acid anhydrides, primary benzylic amines, and aniline derivatives to ca. 200 °C with 3 mL of dry toluene, and 1∼2 mL of triethylamine in high-pressure sealed tubes (Buchi glasuster 0032) to produce cantharidinimides and their analogues in good yields. The para-aminobenzylic imides showed greater inhibition of nitric oxide (NO) synthesis by NO synthase (NOS) than did ortho- and meta-aminobenzylic imides. Compound 3fp, para-aminobenzylic norbonane-imide, had the most potent effect on inducible NOS among the tested compounds and showed 35% inhibition. [ABSTRACT FROM AUTHOR]