We report the in vivo targeting and imaging of tumor vasculature using arginine-glycine-aspartic acid (RGD) peptide-labeled quantum dots (QDs). Athymic nude mice bearing subcutaneous U87MG human glioblastoma tumors were administered QD705-RGD intravenously. The tumor fluorescence intensity reached maximum at 6 h postinjection with good contrast. The results reported here open up new perspectives for integrin-targeted near-infrared optical imaging and may aid in cancer detection and management including imaging-guided surgery.

The aim of the present study was to evaluate the effects on the susceptibility to colorectal cancer (CRC) of genetic polymorphisms in P-glycoprotein (PGP) and the metabolic enzymes cytochrome P450 1A2 (CYP1A2) and flavin-containing monooxygenase 3 (FMO3). We analyzed five single-nucleotide polymorphisms (SNP) in 93 cancer-free volunteers and 111 patients with CRC: one common genetic variant of the PGP-encoding MDR1 gene and four SNP in genes for metabolic enzymes (two SNP in FMO3 and two SNP in CYP1A2). The genotypes and allele frequencies of the MDR1/C3435T, FMO3/G488A, FMO3/A923G and CYP1A2/G-3860 A polymorphisms were not significantly different in cancerfree subjects and CRC patients. However, a significant association was found between the CYP1A2/A-163C polymorphism and the risk of CRC, particularly in elderly (>55 years) subjects and smokers. A phenotyping study in normal smokers showed that the CYP1A2 activity of subjects with the CYP1A2/− − − −163 AA genotype was significantly lower than that of subjects carrying the CYP1A2 (1-6) The carcinogens that cause the development of CRC enter the body as (pro)carcinogens via transporters, (7)(8)(9) and are activated to carcinogens or eliminated by various enzymes.(10) These toxicokinetic-related proteins are also controlled by our genetic background (e.g. by genetic polymorphisms). In considering the effects of genetic polymorphisms on the toxicokinetic profiles of xenobiotics, particularly (pro) carcinogens, we must evaluate the combined effects of genetic polymorphisms in both transporters and metabolic enzymes.To date, numerous studies have been conducted to correlate the genetic polymorphisms of single proteins and the risk of disease development or progression. In particular, genetic polymorphisms in drug metabolizing enzymes, such as the cytochrome P450 1 (CYP1A) family, (11,12) glutathione Stransferases, (13) N-acetyltransferases (14) and UDP-glucuronosyltransferases, (15) are the most well-known and important genetic factors in the development of CRC. Flavin-containing monooxygenase 3 (FMO3) is one of the major hepatic metabolic enzymes that catalyze the NADPH-dependent attachment of molecular oxygen to endogenous and foreign chemicals containing nucleophilic N, S and P heteroatoms. There are few studies of the relationship between FMO3 activity and carcinogenesis. A drug transporter, P-glycoprotein (PGP), is a recognized gatekeeper that limits the accumulation of xenobiotics in the body by facilitating ATPconsuming efflux. Recently, studies of the relationship between MDR1 polymorphisms and disease susceptibility have been conducted. (16,17) However, there has been no report of the relationship between the combined genetic polymorphisms of drug transporters and metabolic enzymes and CRC development.Against this background, we analyzed the common genetic polymorphisms in the genes for the drug transporter MDR1 and the metabolic enzymes CYP1A2 and FMO3, and attempted to elucidate the association between these polymorphisms and sporadic CRC in Koreans. We a...

The circulating peptide hormone hepcidin maintains systemic iron homeostasis. Hepcidin production increases during inflammation and as a result of endoplasmic reticulum (ER) stress. Elevated hepcidin levels decrease dietary iron absorption and promote iron sequestration in reticuloendothelial macrophages. Furthermore, increased plasma hepcidin levels cause hypoferremia and the anemia associated with chronic diseases. The signal transduction pathways that regulate hepcidin during inflammation and ER stress include the IL-6-dependent STAT-3 pathway and the unfolded protein response-associated cyclic AMP response element-binding protein-H (CREBH) pathway, respectively. We show that carbon monoxide (CO) suppresses hepcidin expression elicited by IL-6-and ER-stress agents by inhibiting STAT-3 phosphorylation and CREBH maturation, respectively. The inhibitory effect of CO on IL-6-inducible hepcidin expression is dependent on the suppressor of cytokine signaling-3 (SOCS- 3 IntroductionHepcidin, a circulating peptide hormone synthesized by the liver, functions as a master regulator of iron homeostasis. 1-3 Elevated levels of hepcidin can block the release of iron from macrophages, impair intestinal iron absorption, and cause hypoferremia, leading to iron deficiency anemia. [4][5][6][7] Hepcidin plays a major role in the anemia of inflammation observed in patients with a variety of disorders, including infection, arthritis, inflammatory bowel disease, trauma, cancer, and organ failure. 1,8 IL-6 is the principal regulator of hepcidin expression associated with the anemia of inflammation. 8 In humans, IL-6 can increase hepcidin levels and decrease serum iron levels. IL-6 treatment also induces hepcidin expression in vivo and in primary hepatocytes and hepatoma cell lines. The critical role of IL-6 in hepcidin expression is illustrated by experiments showing that anti-IL-6 Abs block hepcidin mRNA expression in vivo and in hepatocytes stimulated by lipopolysaccharide (LPS). 9 Furthermore, IL-6-deficient mice display impaired hepcidin induction and do not display low serum iron in response to pro-inflammatory stimuli. 9 These observations suggest a relationship between IL-6 and the expression of hepcidin in inflammation.IL-6 plays a central role in the regulation of the acute-phase response (APR) in hepatocytes. 10 After exposure to pro-inflammatory stimuli, IL-6 is released and binds to a complex of the IL-6 receptor-␣ and gp130. 11 The IL-6 ligand-receptor interaction results in the activation of JAKs, which in turn activate STAT-3 by tyrosine (Y705) phosphorylation. Phosphorylated STAT-3 subsequently translocates into the nucleus, where it regulates the transcription of target genes including hepcidin. 12 The transcriptional activity of STAT-3 is regulated by serine (S727) phosphorylation. Additional factors appear to regulate hepcidin expression, because IL-6-knockout mice maintain some hepcidin responsiveness to LPS. For example, IL-1 has been shown to stimulate hepcidin expression in both mouse hepatocytes and human Huh...

No abstract

Synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been reported to exhibit anti-invasive and anti-metastatic activities by suppressing the enzymatic activity of matrix metalloproteinase (MMP)-9, but the underlying mechanism remains unclear. Here, we show that 4-HPR blocks the activity of MMP-9 in two ways: by reducing phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 secretion and by suppressing cell invasion through the downregulation of MMP-9 gene transcription in MCF-7 breast cancer cells. 4-HPR inhibits the transcriptional activity of MMP-9 by reducing the DNA-binding activity of NF-κB on the MMP-9 promoter as well as by inhibiting the degradation of IκBα, leading to cytoplasmic accumulation of NF-κB. We also found that 4-HPR inhibits invasion and MMP-9 expression in the highly metastatic breast cancer cell line MDA-MB-231. Thus, 4-HPR might be a potent anti-invasive agent that works by suppressing MMP-9 expression via the NF-κB signaling pathway.

This study presents a novel droplet-jet mode of near-field electrospinning which allows microscale control of helix patterns using nanofiber. While the cone-jet mode has been used to generate a printable nanofiber to date, the cone-jet mode requires a high applied voltage with a long jet travel distance to obtain the nanofiber, resulting in a large coiling diameter. In order to integrate the near-field electrospinning into microscale devices, it is important to achieve a comparable nanofiber pattern resolution. Herein, we have demonstrated printing of nanofibers with a coiling diameter of sub-10 µm, which is produced by the droplet-jet mode of near-field electrospinning. Also, it is found that the coiling diameter, wavelength, and frequency can be controlled by the droplet size as one of the process parameters in the droplet-jet mode. The droplet-jet mode will be a promising near-field electrospinning technique to apply directwritten nanofibers to various micro-scale applications.

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Silver dimetal chalcogenide (Ag-V-VI ) ternary quantum dots (QDs) are emerging lead-free materials for optoelectronic devices due to their NIR band gaps, large absorption coefficients, and superior electronic properties. However, thin film-based devices of the ternary QDs still lag behind due to the lack of understanding of the surface chemistry, compared to that of lead chalcogenide QDs even with the same crystal structure. Herein the surface ligand interactions of AgSbS QDs, synthesized with 1-dodecanethiol used as a stabilizer, are studied. For nonpolar (1 0 0) surfaces, it is suggested that the thiolate ligands are associated with the crystal lattices, thus preventing surface oxidation by protecting sulfur after air-exposure, as confirmed through optical and surface chemical analysis. Otherwise, silver rich (1 1 1) surfaces are passivated by thiolate ligands, allowing ligand exchange processes for the conductive films. This in-depth investigation of the surface chemistry of ternary QDs will prompt the performance enhancement of their optoelectronic devices.