A small ubiquitin-related modifier-interacting motif functions as the transcriptional activation domain of Krüppel-like factor 4.

The zinc finger transcription factor, Krüppel-like factor 4 (KLF4), regulates numerous biological processes, including proliferation, differentiation, and embryonic stem cell self-renewal. Although the DNA sequence to which KLF4 binds is established, the mechanism by which KLF4 controls transcription is not well defined. Small ubiquitin-related modifier (SUMO) is an important regulator of transcription.

Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration.

This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity--properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions.

Tissue-engineered fascia from vaginal fibroblasts for patients needing reconstructive pelvic surgery.

Introduction And Hypothesis: Mesh-augmented reconstructive surgery for pelvic organ prolapse (POP) does not meet clinical expectations. A tissue-engineered fascia equivalent needs to be developed.

Methods: Human vaginal fibroblasts (HVFs) from 10 patients were characterized in vitro.

The magnetophoretic mobility and superparamagnetism of core-shell iron oxide nanoparticles with dual targeting and imaging functionality.

With the goal to achieve highly efficacious MRI-monitored magnetic targeting, a novel drug carrier with dual nature of superior magnetophoretic mobility and superparamagnetism was synthesized. This carrier was specially designed in a core-shell structure. The core was achieved by utilizing a strategy of self-assembly of oppositely charged ultrafine superparamagnetic iron oxide nanoparticles previously prepared.

Optimized speckle variance OCT imaging of microvasculature.

We optimize speckle variance optical coherence tomography (svOCT) imaging of microvasculature in high and low bulk tissue motion scenarios. To achieve a significant level of image contrast, frame rates must be optimized such that tissue displacement between frames is less than the beam radius. We demonstrate that higher accuracy estimates of speckle variance can enhance the detection of capillaries.

Near IR heptamethine cyanine dye-mediated cancer imaging.

Purpose: Near-IR fluorescence imaging has great potential for noninvasive in vivo imaging of tumors. In this study, we show the preferential uptake and retention of two hepatamethine cyanine dyes, IR-783 and MHI-148, in tumor cells and tissues.

Experimental Design: IR-783 and MHI-148 were investigated for their ability to accumulate in human cancer cells, tumor xenografts, and spontaneous mouse tumors in transgenic animals.

An ELISA for quantification of T84.66, a monoclonal anti-CEA antibody, in mouse plasma.

T84.66 is a monoclonal antibody with high affinity and specificity for tumor-associated carcinoembryonic antigen (CEA). In this work, we have developed an enzyme linked immunosorbent assay to determine T84.

Genetic and Chemical Models of Colorectal Cancer in Mice.

Colorectal cancer (CRC) is a significant health concern because of its associated mortality. Most CRCs exhibit dysregulation of the Wnt signaling pathway, caused by mutational inactivation of the adenomatous polyposis coli tumor suppressor gene (APC) or mutational activation of β-catenin. Disease progression is accompanied by additional mutations in the KRAS oncogene and p53 tumor suppressor gene.

Krüppel-like factor 5 is a crucial mediator of intestinal tumorigenesis in mice harboring combined ApcMin and KRASV12 mutations.

Background: Both mutational inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene and activation of the KRAS oncogene are implicated in the pathogenesis of colorectal cancer. Mice harboring a germline ApcMin mutation or intestine-specific expression of the KRASV12 gene have been developed. Both mouse strains develop spontaneous intestinal tumors, including adenoma and carcinoma, though at a different age.

Doppler optical coherence tomography for interventional cardiovascular guidance: in vivo feasibility and forward-viewing probe flow phantom demonstration.

We demonstrate the potential of a forward-looking Doppler optical coherence tomography (OCT) probe for color flow imaging in several commonly seen narrowed artery morphologies. As a proof of concept, we present imaging results of a surgically exposed thrombotic occlusion model that was imaged superficially to demonstrate that Doppler OCT can identify flow within the recanalization channels of a blocked artery. We present Doppler OCT images in which the flow is nearly antiparallel to the imaging direction.

In situ 24 kHz coherent imaging of morphology change in laser percussion drilling.

We observe sample morphology changes in real time (24 kHz) during and between percussion drilling pulses by integrating a low-coherence microscope into a laser micromachining platform. Nonuniform cut speed and sidewall evolution in stainless steel are observed to strongly depend on assist gas. Interpulse morphology relaxation such as hole refill is directly imaged, showing dramatic differences in the material removal process dependent on pulse duration/peak power (micros/0.

Wavelength-swept spectral and pulse shaping utilizing hybrid Fourier domain modelocking by fiber optical parametric and erbium-doped fiber amplifiers.

We report the first Fourier domain modelocked (FDML) laser constructed using optical parametric amplifier (OPA) in conjunction with an erbium-doped fiber amplifier (EDFA), centered at approximately 1555 nm, to the best of our knowledge. We utilize a one-pump OPA and a C-band EDFA in serial configuration with a tunable Fabry-Perot interferometer to generate a hybrid FDML spectrum. Results demonstrate a substantially better spectral shape, output power and stability than individual configurations, with decreased sensitivity to polarization changes.

Specific down regulation of 3T3-L1 adipocyte differentiation by cell-permeable antisense HIF1alpha-oligonucleotide.

Hypoxia is a strong modulator of angiogenesis, accelerating adipose tissue expansion, suggesting that hypoxia inducible factor 1alpha (HIF1alpha) can be a novel target for anti-obesity. We conjugated antisense-HIF1alpha-oligonucleotide (ASO) with low molecular weight protamine (LMWP), a cell-penetrating peptide, to enhance its ability to block hypoxic-angiogenesis, thereby eliciting an anti-obesity effect. Nano-sized ASO-LMWP (AS-L) conjugates enhanced cellular uptake of ASO without yielding a cytotoxic effect and protected the ASO against enzymatic attack and chemical reduction.

In vivo endoscopic multi-beam optical coherence tomography.

A multichannel optical coherence tomography (multi-beam OCT) system and an in vivo endoscopic imaging probe were developed using a swept-source OCT system. The distal optics were micro-machined to produce a high numerical aperture, multi-focus fibre optic array. This combination resulted in a transverse design resolution of <10 microm full width half maximum (FWHM) throughout the entire imaging range, while also increasing the signal intensity within the focus of the individual channels.

p53 suppresses structural chromosome instability after mitotic arrest in human cells.

The p53 tumor suppressor inhibits the proliferation of cells that undergo prolonged activation of the mitotic checkpoint. However, the function of this antiproliferative response is not well defined. Here, we report that p53 suppresses structural chromosome instability after mitotic arrest in human cells.

Oxygen-independent degradation of HIF-alpha via bioengineered VHL tumour suppressor complex.

Tumour hypoxia promotes the accumulation of the otherwise oxygen-labile hypoxia-inducible factor (HIF)-alpha subunit whose expression is associated with cancer progression, poor prognosis and resistance to conventional radiation and chemotherapy. The oxygen-dependent degradation of HIF-alpha is carried out by the von Hippel-Lindau (VHL) protein-containing E3 that directly binds and ubiquitylates HIF-alpha for subsequent proteasomal destruction. Thus, the cellular proteins involved in the VHL-HIF pathway have been recognized as attractive molecular targets for cancer therapy.

Comparison of electron spin resonance spectroscopy and inductively-coupled plasma optical emission spectroscopy for biodistribution analysis of iron-oxide nanoparticles.

Magnetic nanoparticles (MNP) have been widely studied for use in targeted drug delivery. Analysis of MNP biodistribution is essential to evaluating the success of targeting strategies and the potential for off-target toxicity. This work compared the applicability of inductively coupled plasma optical emission spectroscopy (ICP-OES) and electron spin resonance (ESR) spectroscopy in assessing MNP biodistribution.

Caffeic acid phenethyl ester inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using a local delivery system.

Over the last two decades, significant advances have been made in percutaneous coronary intervention (PCI) for the treatment of atherosclerotic plaques. However, restenosis after PCI still challenges both vascular biologists and interventional cardiologists. In this study, we found that caffeic acid phenethyl ester (CAPE) displayed an inhibitory effect on human coronary smooth muscle cell (HCSMC) growth and migration.

The systemic delivery of siRNAs by a cell penetrating peptide, low molecular weight protamine.

Small interfering RNAs (siRNAs), used for specific down-regulation of targeted genes, have garnered considerable interest as an attractive new class of drugs for broad clinical applications. The polyanionic charges carried by these siRNAs, however, restrain cellular uptake and consequently limit effects on gene regulation. Herein the authors describe a peptide/siRNA complex containing the cell penetrating peptide derived from natural protamine, termed low molecular weight protamine (LMWP), for the treatment of cancer.

Altered fibrinolytic activities in gastric cancer and uremic patients after intervention.

Introduction: Although thromboembolism is the most recognized cause of death in cancer and uremic patients following tumorectomy or hemodialysis, respectively, little data exist concerning its etiologies and treatments in post-intervention settings. In this study, we determined the post-intervention fibrinolytic activities to exploit their implications in gastric cancer and uremic patients.

Materials And Methods: A small-scale case-control study with totally 56 cases aimed to compare the difference of the post-intervention fibrinolytic activities of two hypercoagulable groups of gastric cancer and uremic patients versus healthy controls was conducted.

Intradiscal injection of simvastatin retards progression of intervertebral disc degeneration induced by stab injury.

Introduction: Earlier work indicates that the cholesterol-lowering drug, simvastatin, is anabolic to chondrogenic expression of rat intervertebral disc (IVD) cells, which suggests a potential role for simvastatin in IVD regeneration. In this study, we expand on our earlier work to test the effectiveness of simvastatin on disc degeneration utilizing a rat tail disc degeneration model.

Methods: 30 rats that underwent 21 G needle-puncture at rat tail discs were injected with simvastatin-loaded poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG) gel (5 mg/ml) or vehicle control at 4 weeks after needle injury.

Role of prolonged mitotic checkpoint activation in the formation and treatment of cancer.

Mitotic abnormalities are a common feature of human cancer cells, and recent studies have provided evidence that such abnormalities may play a causative, rather than merely incidental role, in tumorigenesis. One such abnormality is prolonged activation of the mitotic checkpoint, which can be provoked by a number of the gene changes that drive tumor formation. At the same time, antimitotic chemotherapeutics exert their clinical efficacy through the large-scale induction of prolonged mitotic checkpoint activation, indicating that mitotic arrest is influential in both the formation and treatment of human cancer.

PEGylation of bacterial cocaine esterase for protection against protease digestion and immunogenicity.

Enhancing cocaine metabolism by administration of cocaine esterase (CocE) has been considered as a promising treatment strategy for cocaine overdose and addiction, as CocE is the most efficient native enzyme yet identified for metabolizing the naturally occurring cocaine. A major obstacle to the clinical application of CocE, however, lies in its thermo-instability, rapid degradation by circulating proteases, and potential immunogenicity. PEGylation, namely by modifying a protein or peptide compound via attachment of polyethylene glycol (PEG) chains, has been proven to overcome such problems and was therefore exploited in this CocE investigation.