Muscone derivative ZM-32 inhibits breast tumor angiogenesis by suppressing HuR-mediated VEGF and MMP9 expression.

Inhibition of tumor angiogenesis is a highly effective strategy for cancer treatment. Human antigen R (HuR), an RNA-binding protein, is overexpressed in many cancers and regulates the mRNAs of multiple angiogenic factors by binding to the adenylate-uridylate-rich element in their 3' untranslated region. HuR protein has been demonstrated to be an important regulatory factor in macrophage-mediated angiogenesis, a process in which macrophages are critical for tumor progression. Muscone is a synthetic equivalent of musk, and recent studies have shown that it has a regulatory effect on angiogenesis. In this study, we synthesized five series of muscone derivatives and discovered that compound ZM-32 was effective in preventing HuR RRM1/2-Vegf-a mRNA complex formation. ZM-32 bound to HuR RRM1/2 protein with a KD value of 521.7 nmol/L. Furthermore, ZM-32 inhibited endothelial cell proliferation, migration, and tubule formation, and suppressed the VEGF/VEGFR2/ERK1/2 signaling axis mediated by macrophages in vitro. We also demonstrated that ZM-32 effectively prevented the proliferation and migration of breast cancer cells and inhibited the growth and angiogenesis of MDA-MB-231 xenograft tumors without any obvious toxicity in vivo. Mechanistically, exposure to ZM-32 influenced the mRNA stability of Vegf-a and Mmp9 in a HuR-dependent manner in both macrophages and MDA-MB-231 cells. Thus, in this study we identified a new muscone derivative, ZM-32, with anti-angiogenesis effects mediated via targeting HuR in breast cancer, that may become a potentially valuable lead compound for anti-cancer angiogenesis.

Co-administration of Shexiang Baoxin Pill and Chemotherapy Drugs Potentiated Cancer Therapy by Vascular-Promoting Strategy.

Effective delivery of chemotherapeutic agents to tumors is a critical objective of improved cancer therapy. Traditional antiangiogenic therapy aims at eradicating tumor blood vessels, but the subsequently reduced blood perfusion may limit the drug amount delivered into the tumor and potentially lead to tumor hypoxia, which has been proved to be unable to meet the therapeutic expectations. "Shexiang Baoxin Pill" (SBP) is a well-known traditional Chinese medicine (TCM) used in clinical treatment of cardiovascular diseases, which has the pharmacological effect of pro-angiogenesis demonstrated recently. In this study, we disclosed our finding that SBP could enhance the effective treatment performance of gemcitabine (GEM) while minimizing the toxic side effects caused by GEM. Mechanistically, SBP increased tumor angiogenesis, blood perfusion, vascular permeability, and vessel dilation, which subsequently favored the delivery of GEM to the tumor lesion. Moreover, combined treatment with SBP and GEM could modify tumor microenvironment and consequently overcome multidrug resistance, and this combination therapy is also suitable for combination of SBP with some other chemotherapeutic drugs as well. These results suggest that combining SBP with chemotherapeutic agents achieves better treatment efficiency, which can open an avenue for expanding the combined treatment of anti-cancer chemotherapeutic drugs with TCM.

Hot-compressed water extraction of polysaccharides from soy hulls.

The polysaccharides of soy hulls were extracted by hot-compressed water at temperatures of 110 from 180°C and various treatment times (10-150min) in a batch system. It was determined that a moderate temperature and short time are suitable for the preparation of polysaccharides. The structure of xylan and the inter- and intra-chain hydrogen bonding of cellulose fibrils in the soy hulls were not significantly broken down. The polysaccharides obtained were primarily composed of α-L-arabinofuranosyl units, 4-O-methyl-glucuronic acid units and α-D-galactose units attached with substituted units. A sugar analysis indicated that arabinose was the major component, constituting 35.6-46.9% of the polysaccharide products extracted at 130°C, 140°C, and 150°C. This investigation contributes to the knowledge of the polysaccharides of soy by-products, which can reduce the environmental impact of waste from the food industries.

[Clinical analysis on 75 cases of aluminosis caused by black fused alumina].

OBJECTIVE: To investigate the hazards of aluminum dusts to the exposed workers and the clinical features of aluminosis. METHOD: Retrospective investigation on 75 aluminosis patients from a certain factory diagnosed in Shanghai Occupational Diseases Hospital from 1972 to 2004 was carried out. RESULTS: There were 27 cases of aluminosis I (36.0%), 28 cases of aluminosis II (37.3%) and 20 cases of aluminosis III (26.7%) among 75 cases. The shortest exposure duration was 3 years, and the longest 17 years, and 37 cases of aluminosis occurred after exposure less than 10 years. hest radiographic examination mainly showed irregular micro-shadows: t (22/75), s (4/75), t/u (1/75), t/s (2/75), or predominantly irregular mixed microshadows s/p (5/75), s/r (1/75), t/p (9/75), t/q (5/75); some showed round shape micro-shadows: p (6/75), q (1/75), p/q (3/75), q/p (1/75). 27 cases showed large shadows, 20 cases of them were diagnosed as pneumoconiosis III. A lot of irregular micro-shadows gathered and developed to form uneven, loose and border-irregular masses. Most massive fibrosis looked like stripe or plait, located mostly in middle and upper lung field. 8 patients suffered from aluminosis with single side of massive fibrosis and 12 with both sides of massive fibrosis, accounting for 40% and 60% respectively. Mediastinal and bronchopulmonary lymph nodes were enlarged and calcified, accompanied with pleural thickening. CONCLUSIONS: Short exposure to high concentration of black fused alumina may cause serious aluminosis to the exposes. The hazards of aluminum dusts should not be ignored.