Impact of HER2 on prognosis and benefit from adjuvant chemotherapy in stage II/III gastric cancer patients: a multicenter observational study.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a well-developed therapeutic target in breast and gastric cancer (GC). However, the impact of HER2 on survival and benefit from fluorouracil-based adjuvant chemotherapy remains unclear in patients with GC. MATERIALS AND METHODS: This multicenter cohort study involved 5622 consecutive stage II/III GC patients. HER2 expression was assessed prospectively via immunohistochemistry (IHC). The staining intensity was graded on a scale of 0 to 3+. An IHC score of 2+or 3+was defined as high expression, and a score of 3+was defined as overexpression. RESULTS: HER2 overexpression was independently associated with a lower 5-year overall survival (OS) in stage II [hazard ratio (HR), 2.10; 95% CI: 1.41-3.11], but not in stage III GC (HR, 1.00; 95% CI, 0.82-1.20). Further analysis revealed that stage II patients with high HER2 expression showed a poorer response to chemotherapy than stage II patients with low HER2 expression ( Pinteraction =0.024). The HRs for 5-year OS were 0.51 (95% CI, 0.38-0.70) for stage II patients with low HER2 expression, 0.58 (95% CI, 0.51-0.66) for stage III patients with low HER2 expression, 1.13 (95% CI, 0.61-2.09) for stage II patients with high HER2 expression, and 0.47 (95% CI, 0.36-0.61) for stage III patients with high HER2 expression. CONCLUSIONS: Fluorouracil-based adjuvant chemotherapy is insufficient for stage II GC patients with high HER2 expression, indicating that prospective trials are required to validate alternative HER2-targeted adjuvant therapies in the individuals above.

A new cytotoxic biflavonoid from the rhizome of Wikstroemia indica.

One new chalcone-flavone biflavonoid, 3'-hydroxydaphnodorin A (1), together with 12 known biflavonoids (2-13), was isolated from the rhizome of Wikstroemia indica. Their structures were established on the basis of extensive spectroscopic methods. Eight isolated compounds 1-3, 6, 7, 9, 12 and 13 were evaluated for their cytotoxic activities against cancer-derived cell lines Hep3B, HepG2 and CNE2, and 1 was found to possess moderate cytotoxicity against HepG2 and CNE2 cell lines, with IC50 values of 65.5 ± 11.4 and 53.6 ± 10.1 µM, respectively.

Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of ß-Arrestin 2-Mediated Pathways in Hippocampus.

Xiao Yao San (XYS) is a classical Chinese medicine formula that has been widely used to treat mood disorders for hundreds of years. To confirm the effect of XYS and better understand its underlying mechanism, high-performance liquid chromatography-mass spectrometry analysis-based quality control of XYS extracts and proteomics-based identification of differential proteins in the hippocampus were adopted in social isolation and chronic unpredictable mild stress- (CUMS-) treated rats. The depressive-like behavior of rats induced by CUMS resembled the manifestation of human depression. The upregulated corticosterone (CORT) and urocortin 2 (UCN2) levels demonstrated the existence of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT. XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of ß-arrestin 2. The expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and mammalian target of rapamycin (mTOR) were also elevated by XYS. In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2. The upregulation of BDNF/TrkB and the phosphorylation of mTOR require ß-arrestin 2 as a scaffold to regulate stress signaling.

Two pairs of enantiomeric neolignans from Lobelia chinensis.

A pair of new enantiomeric neolignans, ethyl 3-[(2R,3S)-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl] propanoate (+) (1) and ethyl 3-[(2S,3R)-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl] propanoate (-) (1), together with a pair of known enantiomeric neolignans (+) (2) and (-) (2), as well as five known lignans (3-7) were isolated from the ethanol extract of Lobelia chinensis. Their structures were elucidated on the basis of extensive spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS and CD spectra.

[Chemical constituents from leaves of Morus multicaulis].

OBJECTIVE: To study the chemical constituents from the leaves of Morus multicaulis. METHOD: The compounds were isolated by ion exchange resin, silica gel and Sephadex LH -20 column chromatographies. Their structures were elucidated on the basis of physico-chemical properties and spectral data. RESULT: Twelve compounds were isolated from the leaves of this plant. Their structures were identified as 1-deoxynojirimycin (1), fagomine (2), 2-O-alpha-D-galactopyranosyl-1-deoxynojirimycin (3), quercetin-7-O-beta-D-glucoside (4), kaempferol (5), quercetin (6), scopoletin (7), D-aspartic acid (8), L-proline (9), D-alpha-alanine (10), myo-inositol (11) and dausterol (12). CONCLUSION: All compounds were isolated from this plant for the first time.