We report a coaxial fiber supercapacitor, which consists of carbon microfiber bundles coated with multiwalled carbon nanotubes as a core electrode and carbon nanofiber paper as an outer electrode. The ratio of electrode volumes was determined by a half-cell test of each electrode. The capacitance reached 6.3 mF cm(-1) (86.8 mF cm(-2)) at a core electrode diameter of 230 μm and the measured energy density was 0.7 μWh cm(-1) (9.8 μWh cm(-2)) at a power density of 13.7 μW cm(-1) (189.4 μW cm(-2)), which were much higher than the previous reports. The change in the cyclic voltammetry characteristics was negligible at 180° bending, with excellent cycling performance. The high capacitance, high energy density, and power density of the coaxial fiber supercapacitor are attributed to not only high effective surface area due to its coaxial structure and bundle of the core electrode, but also all-carbon materials electrodes which have high conductivity. Our coaxial fiber supercapacitor can promote the development of textile electronics in near future.

Grain boundaries in graphene are formed by the joining of islands during the initial growth stage, and these boundaries govern transport properties and related device performance. Although information on the atomic rearrangement at graphene grain boundaries can be obtained using transmission electron microscopy and scanning tunnelling microscopy, large-scale information regarding the distribution of graphene grain boundaries is not easily accessible. Here we use optical microscopy to observe the grain boundaries of large-area graphene (grown on copper foil) directly, without transfer of the graphene. This imaging technique was realized by selectively oxidizing the underlying copper foil through graphene grain boundaries functionalized with O and OH radicals generated by ultraviolet irradiation under moisture-rich ambient conditions: selective diffusion of oxygen radicals through OH-functionalized defect sites was demonstrated by density functional calculations. The sheet resistance of large-area graphene decreased as the graphene grain sizes increased, but no strong correlation with the grain size of the copper was revealed, in contrast to a previous report. Furthermore, the influence of graphene grain boundaries on crack propagation (initialized by bending) and termination was clearly visualized using our technique. Our approach can be used as a simple protocol for evaluating the grain boundaries of other two-dimensional layered structures, such as boron nitride and exfoliated clays.

c-myc oncogene is implicated in tumorigenesis of many cancers, including breast cancer. Although c-myc is a well-known estrogen-induced gene, its promoter has no estrogen-response element, and the underlying mechanism by which estrogen induces its expression remains obscure. Recent genome-wide studies by us and others suggested that distant elements may mediate estrogen induction of gene expression. In this study, we investigated the molecular mechanism by which estrogen induces c-myc expression with a focus on these distal elements. Estrogen rapidly induced c-myc expression in estrogen receptor (ER)-positive breast cancer cells. Although estrogen had little effect on c-myc proximal promoter activity, it did stimulate the activity of a luciferase reporter containing a distal 67-kb enhancer. Estrogen induction of this luciferase reporter was dependent upon both a half-estrogen response element and an activator protein 1 (AP-1) site within this enhancer, which are conserved across 11 different mammalian species. Small interfering RNA experiments and chromatin immunoprecipitation assays demonstrated the necessity of ER and AP-1 cross talk for estrogen to induce c-myc expression. TAM67, the AP-1 dominant negative, partially inhibited estrogen induction of c-myc expression and suppressed estrogen-induced cell cycle progression. Together, these results demonstrate a novel pathway of estrogen regulation of gene expression by cooperation between ER and AP-1 at the distal enhancer element and that AP-1 is involved in estrogen induction of the c-myc oncogene. These results solve the long-standing question in the field of endocrinology of how estrogen induces c-myc expression.

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Regulation of phosphoinositides is important to tumorigenesis. PTEN (phosphatase and tensin homologue deleted from chromosome 10) is a dual specificity phosphatase that dephosphorylates the 3Ј-sites of the phosphoinositides PI(3,4)P 2 2 and PI(3,4,5)P 3 (1). Endogenous PI(3,4,5)P 3 levels are also regulated by phosphatidylinositol 3-kinase (PI3K), which phosphorylates the D3 position of phosphatidylinositol (PI) on PI(4)P and PI(4,5)P 2 to produce PI(3,4)P 2 and PI(3,4,5)P 3 . PI(3,4,5)P 3 and PI(3,4)P 2 recruit the pleckstrin homology domains of specific intracellular proteins to the plasma membrane, an essential event in the activation of PI3K-dependent kinases such as phosphoinositide-dependent kinase-1 and protein kinase B/AKT, which have a key role in cellular survival and transformation (2). PI3K-dependent signaling is frequently activated in a variety of tumor types, including non-small cell lung cancer (NSCLC). Several genetic events previously described in NSCLC activate PI3K, including amplification of PIK3CA and activating mutations in PIK3CA, EGFR,. PTEN gene expression is frequently silenced in NSCLC (7), but the mechanisms contributing to the loss of PTEN expression in NSCLC have not been defined. PTEN genetic deletion is a rare event in NSCLC (8), raising the possibility that PTEN is silenced transcriptionally or post-transcriptionally. Of note, PTEN expression is transcriptionally suppressed by tumor necrosis factor-␣ (TNF␣) through NFB (9, 10), a heterodimeric transcription factor that is constitutively activated in NSCLC (7).NFB consists of the transactivation subunit RelA/p65 and the DNA-binding subunits p50 (NFB1) and p52 (NFB2), which are processed from the precursors p105 and p100, respectively (11). In unstimulated conditions, NFB is sequestered in the cytoplasm by inhibitor of NFB (IB) and remains transcriptionally inactive. Upon stimulation by inflammatory cytokines or peptide growth factors, IB is phosphorylated by IB kinase (IKK), a multiprotein complex consisting of two kinase subunits (IKK␣ and IKK␤) and a regulatory subunit (IKK␥/NEMO), and undergoes proteasome-dependent degradation. The released NFB translocates into the nucleus and regulates the expression of target genes with key roles in the prevention of apoptosis, promotion of tumor growth, and activation of inflammatory responses (12).NSCLC cells undergo apoptosis in response to PI3K pathway inhibition (13,14). We previously found that a stress kinase, * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. □ S The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1 The abbreviations used are: PI(3,4)P 2 , phosphatidylinositol 3,4-bisphosphate; PI(3,4,5)P 3 , phosphatidylinositol 3,4,5-trisphosphate; PI(4)P, phosphatidylinositol 4-monophosphate; PI(4,5)P 2 , phosphatidylinositol 4,5-bisphosphate; PI, L-␣-phosphat...

This study appears to provide the preclinical rationale for the development of these EGFR tyrosine kinase inhibitors for the prevention of human breast cancer.

The epidermal growth factor (EGF) and insulin-like growth factor (IGF) signaling pathways are critically involved in cancer development and progression. However, how these two signals cross-talk with each other to regulate cancer cell growth is not clearly understood. In this study, we found that EGF remarkably induced expression of major IGF signaling components, insulin receptor substrate (IRS)-1 and IRS-2, an effect that could be blocked by EGF receptor (EGFR) tyrosine kinase inhibitors. Although both extracellular signal-regulated kinase and c-Jun NH 2 -terminal kinase (JNK) signaling pathways were involved in the EGF up-regulation of IRS-1, the IRS-2 induction by EGF was specifically mediated by JNK signaling. Consistent with this, EGF increased IRS-2 promoter activity, which was associated with recruitment of activator protein-1 (AP-1) transcription factors and was inhibited by blocking AP-1 activity. Moreover, EGF treatment enhanced IGF-I and integrin engagement-elicited tyrosine phosphorylation of IRS and their downstream signaling, such as binding to phosphatidylinositol 3 ¶-kinase regulatory subunit p85. Finally, repressing the induction of IRS-2 levels abolished the EGF enhancement of cell motility, suggesting that increased IRS-2 is essential for the EGF regulation of breast cancer cell migration. Taken together, our results reveal a novel mechanism of cross-talk between the EGF and IGF signaling pathways, which could have implications in therapeutic applications of targeting EGFR in tumors. Because AP-1 activity is involved in breast cancer progression, our work may also suggest IRS-2 as a useful marker for aggressive breast cancer. (Cancer Res 2006; 66(10): 5304-13)

Purpose: We tested whether a selective estrogen receptor modulator (SERM) and a rexinoid are active for prevention and treatment in the mouse mammary tumor virus-neu mouse model of estrogen receptor^negative breast cancer. Experimental Design: For prevention, mice were fed a powdered control diet, the SERM arzoxifene (Arz, 20 mg/kg diet), the rexinoid LG100268 (268, 30 mg/kg diet), or the combination for 60 weeks. In a second prevention study, mice were fed Arz (6 mg/kg diet), 268 (30 mg/kg diet), the combination of Arz and 268, the SERM acolbifene (Acol, 3 mg/kg diet), or the combination of Acol and 268 for 52 weeks. For the treatment studies, mice with tumors were fed combinations of a SERM and 268 for 4 weeks. Results: The rexinoid 268 and the SERMs Arz and Acol, as individual drugs, delayed the development of estrogen receptor^negative tumors. Moreover, the combination of a SERM and 268 was strikingly synergistic, as no tumors developed in any mouse fed the combination of 268 and a SERM. Moreover, this drug combination also induced significant tumor regression when used therapeutically. These drugs did not inhibit transgene expression in vitro or in vivo, and the combination of Arz and 268 inhibited proliferation and induced apoptosis in the tumors. Conclusion: The combination of a rexinoid and SERM should be considered for future clinical trials.Despite the development of selective estrogen receptor (ER) modulators (SERMs), aromatase inhibitors, and the monoclonal antibody trastuzumab (Herceptin), breast cancer still claims >40,000 lives in the U.S. each year (1). Because of the genetic and epigenetic complexities of an invasive cancer, arresting or reversing carcinogenesis at its earliest stages offers an attractive alternative to treating advanced disease (2, 3). However, the realities of the clinic mean that new drugs and new drug combinations are desperately needed for both the prevention and treatment of breast cancer.A number of drugs have been shown to prevent or treat ER+ breast cancer. SERMs such as tamoxifen and raloxifene are effective in women for both prevention (4 -8) and treatment (9). Newer SERMs such as acolbifene (Acol, EM-652) and its prodrug (EM-800) have been used to prevent the development of and to treat established mammary tumors in animal models (10 -12), and caused the disappearance of 60% of human breast cancer tumors in nude mice (13). Acol also showed positive responses in women who failed tamoxifen treatment (14), suggesting the superiority of Acol over tamoxifen in a series of preclinical studies (15). The SERM arzoxifene (Arz) also prevented mammary carcinogenesis in rats (16) and decreased ER expression in humans in a phase 1 chemoprevention trial (17).In addition to the SERMs, retinoids, such as 9-cis-retinoic acid (18,19), or rexinoids [selective ligands for the retinoid X receptors (RXRs)], such as LGD1069 (bexarotene, Targretin; refs. 20, 21) and LG100268 (268; refs. 22, 23), have been reported to prevent and treat mammary tumors in animal models of ER+ breast ...