J. Neurochem. (2012) 120, 842–849. Abstract Endocannabinoids are neuromodulatory lipids that mediate the central and peripheral neural functions. Endocannabinoids have demonstrated their anti‐proliferative, anti‐angiogenic and pro‐apoptotic properties in a series of studies. In the present study, we investigated the levels of two major endocannabinoids, anandamide and 2‐arachidonylglycerol (2‐AG), and their receptors, CB1 and CB2, in human low grade glioma (WHO grade I‐II) tissues, high grade glioma (WHO grade III‐IV) tissues, and non‐tumor brain tissue controls. We also measured the expressions and activities of the enzymes responsible for anandamide and 2‐AG biosynthesis and degradation, that is, N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D (NAPE‐PLD), fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MGL), and diacylglycerol lipase‐alpha (DGL), in the same samples. Liquid chromatography–mass spectometry analysis showed that the levels of anandamide decreased, whereas the levels of 2‐AG increased in glioma tissues, comparing to the non‐tumor controls. The expression levels and activities of NAPE‐PLD, FAAH and MGL also decreased in glioma tissues. Furthermore, quantitative‐PCR analysis and western‐blot analysis revealed that the expression levels of cananbinoid receptors, CB1 and CB2, were elevated in human glioma tissues. The changes of anandamide and 2‐AG contents in different stages of gliomas may qualify them as the potential endogenous biomarkers for glial tumor malignancy.

An elevated level of the free deaminated sialic acid, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), was first discovered in human ovarian cancers (OCs), suggesting that KDN may be an oncodevelopmental antigen (Inoue S, Lin SL, Chang T, Wu SH, Yao CW, Chu TY, Troy FA II, Inoue Y. 1998. J Biol Chem. 273(42):27199-27204). To determine if this unexpected finding was unique to OC, we developed an LC-MS/MS glycomic approach to quantitatively determine the level of free and conjugated forms of KDN, Neu5Ac and Neu5Gc in head and neck cancers of the throat, and in a subpopulation of matched lymph nodes. These findings were correlated with tumor (T), nodal (N), metastatic (M) involvement and the differentiation status of the tumors. The following new findings are reported: (i) The level of free KDN in 49 throat cancers and a subpopulation of 10 regional lymph nodes accounted for 94.5 and 93.3%, respectively, of the total level of KDN (∼2 µg/g); (ii) in marked contrast, the level of free Neu5Ac in throat cancer and lymph nodes accounted for only 6.5 and 5.1% of the total level of Neu5Ac (85 µg/g); (3) The level of Neu5Gc (0.03 µg/g) in throat cancers was 0.30% of the level of Neu5Ac, two-thirds were conjugated and one-third was free. The central importance of these new findings is that the elevated level of free KDN relative to free Neu5Ac and Neu5GC in throat cancers showing no lymphatic metastasis, and which are poorly to moderately differentiated, suggests that free KDN may be useful as a biomarker for detecting some early-stage cancers at biopsy, and be of possible prognostic value in determining the potential degree of malignancy.

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Whilst researches elucidating a diversity of intracellular mechanisms, platinum-resistant epithelial ovarian cancer (EOC) remains a major challenge in the treatment of ovarian cancer. Here we report that Exo70, a key subunit of the exocyst complex, contributes to both innate and acquired cisplatin resistance of EOC. Upregulation of Exo70 is observed in EOC tissues and is related to platinum resistance and progression-free survival of EOC patients. Exo70 suppressed the cisplatin sensitivity of EOC cells through promoting exocytosis-mediated efflux of cisplatin. Moreover, cisplatin-induced autophagy-lysosomal degradation of Exo70 protein by modulating phosphorylation of AMPK and mTOR, thereby reducing the cellular resistance. However, the function was hampered during prolonged cisplatin treatment, which in turn stabilized Exo70 to facilitate the acquired cisplatin resistance of EOC cells. Knockdown of Exo70, or inhibiting exocytosis by Exo70 inhibitor Endosidin2, reversed the cisplatin resistance of EOC cells both in vitro and in vivo. Our results suggest that Exo70 overexpression and excessive stability contribute to innate and acquired cisplatin resistance through the increase in cisplatin efflux, and targeting Exo70 might be an approach to overcome cisplatin resistance in EOC treatment.

Two new compounds, and 2), and 22 known compounds, were identified from the mangrove-forest-derived fungus Penicillium polonicum H175. The structures of these compounds were elucidated by analysis of the high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), 1D and 2D nuclear magnetic resonance (NMR) data. The glucose effect of compounds was evaluated by the glucose assay kit (Invitrogen, A22189).Compound 3 (aspterric acid) exhibited a significant hypoglycemic effect equivalent to the positive drug rosiglitazone (RSG) at 10 μmol/L.