Inhibition of neocortical beta-amyloid (Abeta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in Abeta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain Abeta deposition (-375 microg/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator. This was accompanied by a modest increase in soluble Abeta (1.45% of total cerebral Abeta); APP, synaptophysin, and GFAP levels were unaffected. General health and body weight parameters were significantly more stable in the treated animals. These results support targeting the interactions of Cu and Zn with Abeta as a novel therapy for the prevention and treatment of AD.

Reduced therapeutic efficacy of sorafenib, a first-generation multikinase inhibitor, is often observed during the treatment of advanced hepatocellular carcinoma (HCC). Emodin is an active component of Chinese herbs, and is effective against leukemia, lung cancer, colon cancer, pancreatic cancer, and HCC; however, the sensitizing effect of emodin on sorafenib-based HCC therapy has not been evaluated. Here, we demonstrate that emodin significantly improved the anti-cancer effect of sorafenib in HCC cells, such as HepG2, Hep3B, Huh7, SK-HEP-1, and PLC/PRF5. Mechanistically, emodin inhibits sterol regulatory element-binding protein-2 (SREBP-2) transcriptional activity, which suppresses cholesterol biosynthesis and oncogenic protein kinase B (AKT) signaling. Additionally, attenuated cholesterol synthesis and oncogenic AKT signaling inactivated signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. Furthermore, emodin synergistically increased cell cycle arrest in the G1 phase and apoptotic cells in the presence of sorafenib. Animal models xenografted with HepG2 or SK-HEP-1 cells also showed that the combination of emodin and sorafenib was sufficient to inhibit tumor growth. Overall, these results suggested that the combination of emodin and sorafenib may offer a potential therapy for patients with advanced HCC.

Several studies suggest that delay in the surgical treatment of breast cancer is significantly associated with lower survival. This study evaluated the tumor growth rate (TGR) of invasive breast cancers during wait times for surgery quantitatively using ultrasonography (US) and identified clinicopathologic factors associated with TGR.This retrospective study was approved by our institutional review board and the requirement for written informed consent was waived. Between August 2013 and September 2014, a total of 323 unifocal invasive breast cancers in 323 women with serial US images at the time of diagnosis and surgery were included. Tumor diameters and volumes were measured using 2-orthogonal US images. TGR during wait times for surgery was quantified as specific growth rates (SGR; %/day) and was compared with clinicopathologic variables using univariate and multivariate analyses.Median time from diagnosis to surgery was 31 days (range, 8–78 days). Maximum tumor diameters and volumes at the time of surgery (mean, 15.6 mm and 1.6 cm3) were significantly larger than at diagnosis (14.7 mm and 1.3 cm3) (P < 0.001). On multivariate analysis, surrogate molecular subtype was a significant independent factor of SGR (P = 0.001); triple negative cancers showed the highest SGR (1.003%/day) followed by HER2-positive (0.859 %/day) and luminal cancers (luminal B, 0.208 %/day; luminal A, 0.175%/day) (P < 0.001). Clinical T stage was more frequently upgraded in nonluminal (triple negative, 18% [12/67]; HER2-positive, 14% [3/22]) than luminal cancers (luminal B, 3% [1/30]; luminal A, 2% [4/204]) (P < 0.001).Invasive breast cancers with aggressive molecular subtypes showed faster TGR and more frequent upgrading of clinical T stage during wait times for surgery.

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