Aberrant activation of Notch receptors has been shown to cause mammary tumors in mice. We therefore used in situ hybridization to analyze expression of Notch ligands and receptors in human breast cancer. High levels of JAG1 and NOTCH1 were noted in a subset of tumors with poor prognosis pathologic features (P < 0.05). We therefore used tissue microarrays to analyze the expression of these genes in a collection of breast cancers from patients representing a wide spectrum of clinical stages, and from whom associated followup survival data was available (n = 184). Patients with tumors expressing high levels of JAG1 or NOTCH1 had a significantly poorer overall survival compared with patients expressing low levels of these genes [5-year survival rate of 42% versus 65% and median survival of 50 versus 83 months, respectively, for JAG1Hi vs. Lo (P = 0.01); 49% versus 64% and 53 versus 91 months, respectively, for NOTCH1Hi vs. Lo (P = 0.02)]. Moreover, a synergistic effect of high-level JAG1 and high-level NOTCH1 coexpression on overall survival was observed (5-year survival rate of 32% and median survival of 40 months; P = 0.003). These data (a) identify novel prognostic markers for breast cancer, (b) suggest a mechanism whereby Notch is activated in aggressive breast tumors, and (c) may identify a signaling pathway activated in poor prognosis breast cancer which can be therapeutically targeted. (Cancer Res 2005; 65(18): 8530-37)

No abstract

Rab is a family of small Ras-like GTPases regulating intracellular vesicle transport. We have previously reported that prenylated Rab acceptor or PRA1 interacts with Rab GTPases and vesicle-associated membrane protein (VAMP2). Structural prediction programs suggest that PRA1, with its two extensive hydrophobic domains, is likely to be an integral membrane protein. However, subcellular fractionation and immunocytochemical analyses indicated that PRA1 is localized both in the cytosol and tightly associated with the membrane compartment. The membrane-bound form can be partially extracted with physiological buffer and urea, suggesting that PRA1 is an extrinsic membrane protein.Deletion of the carboxyl-terminal domain resulted in a protein that behaved as an integral membrane protein, indicating that this domain plays an essential role in maintaining PRA1 in a soluble state. PRA1 can also bind weakly to GDP dissociation inhibitor (GDI), a protein involved in the solubilization of membrane-bound Rab GTPases. Addition of PRA1 inhibited the extraction of membrane-bound Rab3A by GDI, suggesting that membrane localization of Rab GTPases is dependent on the opposing action of PRA1 and GDI. The binding of Rab and VAMP2 to PRA1 is mutually exclusive such that Rab3A can displace VAMP2 in a preformed VAMP2-PRA1 complex.

Our results showed that baicalin possesses an analgesic effect in carrageenan-evoked thermal hyperalgesia. The possible mechanisms of action of baicalin may be associated with the inhibition of proinflammatory mediator overproduction, including cytokines, nitric oxide, and prostaglandin E(2), as well as neutrophil infiltration. This implies that baicalin may be a potential therapeutic analgesic for inflammatory pain.

Sputtered Ba1−xSrxTiO3 (BST) and SrTiO3 (STO) films and capacitors made with these dielectrics have been characterized with respect to physical and electrical properties. Specific capacitance values included a high of 96 fF/μm2 for BST films deposited of 600 °C and a high of 26 fF/μm2 for STO films deposited at 400 °C. Leakage current densities at 3.3 V for the most part varied from mid 10−8 to mid 10−6 A/cm2. All of the dielectrics are polycrystalline, although the lowest temperature STO films have a nearly amorphous layer which impacts their capacitance. Grain size increases with deposition temperature, which correlates to higher dielectric constants. The lattice parameter of the BST films is larger than that of bulk samples. Capacitance, leakage, breakdown, and lifetime results are reported.