In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh.

As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism.

Molecularly targeted nanoparticles: an emerging tool for evaluation of expression of the receptor for advanced glycation end products in a murine model of peripheral artery disease.

Background: Molecular imaging with molecularly targeted probes is a powerful tool for studying the spatio-temporal interactions between complex biological processes. The pivotal role of the receptor for advanced glycation end products (RAGE), and its involvement in numerous pathological processes, aroused the demand for RAGE-targeted imaging in various diseases. In the present study, we evaluated the use of a diagnostic imaging agent for RAGE quantification in an animal model of peripheral artery disease, a multimodal dual-labeled probe targeted at RAGE (MMIA-CML).

Quantitative imaging of the receptor for advanced glycation end-products in prostate cancer.

Purpose: Current screening and monitoring of prostate cancer (PCa) is insufficient, producing inaccurate diagnoses. Presence of the receptor for advanced glycation end-products (RAGE) is associated with signature characteristics of PCa development such as cell proliferation, anchorage-independent growth, angiogenesis, migration, invasion, and poor patient survival. Therefore, we developed a preclinical multimodal imaging strategy targeted at RAGE to diagnose and monitor PCa.

Aberrant Expression of a Non-muscle RBFOX2 Isoform Triggers Cardiac Conduction Defects in Myotonic Dystrophy.

Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by the CTG repeat expansion in the 3'-untranslated region of DMPK gene. Heart dysfunctions occur in ∼80% of DM1 patients and are the second leading cause of DM1-related deaths. Herein, we report that upregulation of a non-muscle splice isoform of RNA-binding protein RBFOX2 in DM1 heart tissue-due to altered splicing factor and microRNA activities-induces cardiac conduction defects in DM1 individuals.

Imaging the Landmarks of Vascular Recovery.

: Peripheral arterial disease (PAD) is a major worldwide health concern. Since the late 1990s therapeutic angiogenesis has been investigated as an alternative to traditional PAD treatments. Although positive preclinical results abound in the literature, the outcomes of human clinical trials have been discouraging.

Multimodal imaging of the receptor for advanced glycation end-products with molecularly targeted nanoparticles.

The receptor for advanced glycation end-products (RAGE) is central to multiple disease states, including diabetes-related conditions such as peripheral arterial disease (PAD). Despite RAGE's importance in these pathologies, there remains a need for a molecular imaging agent that can accurately assess RAGE levels . Therefore, we have developed a multimodal nanoparticle-based imaging agent targeted at RAGE with the well-characterized RAGE ligand, carboxymethyllysine (CML)-modified human serum albumin (HSA).

Multidimensional Clutter Filter Optimization for Ultrasonic Perfusion Imaging.

Combinations of novel pulse-echo acquisitions and clutter filtering techniques can improve the sensitivity and the specificity of power Doppler (PD) images, thus reducing the need for exogenous contrast enhancement. We acquire echoes following bursts of Doppler pulse transmissions sparsely applied in regular patterns over long durations. The goal is to increase the sensitivity of the acquisition to slow disorganized patterns of motion from the peripheral blood perfusion.

Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1.

Cancer stem cells (CSCs) are progenitor cells that contribute to treatment-resistant phenotypes during relapse. CSCs exist in specific tissue microenvironments that cell cultures and more complex models cannot mimic. Therefore, the development of new approaches that can detect CSCs and report on specific properties (e.

Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral angiogenesis in diabetic mice.

The α  β integrin plays an important role in many physiological functions and pathological disorders. α  β is minimally expressed in normal quiescent endothelial cells, but significantly upregulated during neovascularization. In this study, we evaluated a Cu-labeled dimeric cRGD tracer targeted at α  β integrin and report its applicability to assess peripheral angiogenesis in diabetes mellitus (DM).

A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia.

Hypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia. Thus, detection of hypoxia can guide treatment planning and serve as a predictor of patient prognosis. Unfortunately, current methods suffer from invasiveness, poor resolution and low specificity.

Multimodal Assessment of Mesenchymal Stem Cell Therapy for Diabetic Vascular Complications.

Peripheral arterial disease (PAD) is a debilitating complication of diabetes mellitus (DM) that leads to thousands of injuries, amputations, and deaths each year. The use of mesenchymal stem cells (MSCs) as a regenerative therapy holds the promise of regrowing injured vasculature, helping DM patients live healthier and longer lives. We report the use of muscle-derived MSCs to treat surgically-induced hindlimb ischemia in a mouse model of type 1 diabetes (DM-1).

Melanoma topology reveals a stem-like phenotype that promotes angiogenesis.

Tumor angiogenesis provides critical nutrients for cancer progression and may also facilitate pathways for dissemination during the process of metastasis. It is well established that cells that metastasize display characteristics of stem cells; however, the prevailing paradigm points to these stem-like cells residing in the hypoxic niche within the tumor interior. Controlling the geometry at the interface of a population of melanoma cells reveals a role for perimeter topology in promoting a stem-like state with enhanced tumorigenicity.

Expanding Acquisition and Clutter Filter Dimensions for Improved Perfusion Sensitivity.

A method is explored for increasing the sensitivity of power-Doppler imaging without contrast enhancement. We acquire 1-10 s of echo signals and arrange it into a 3-D spatiotemporal data array. An eigenfilter developed to preserve all three dimensions of the array yields power estimates for blood flow and perfusion that are well separated from tissue clutter.

Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a Dimeric-cRGD Peptide for Targeted Imaging of α β Integrin Activity.

Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α β integrin. We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of α β activity (a radiolabeled version, Cu-NOTA-PEG-cRGD, for PET imaging, and a fluorescent version, FITC-PEG-cRGD, for in vitro work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis.

Spatially-resolved metabolic cooperativity within dense bacterial colonies.

Background: The exchange of metabolites and the reprogramming of metabolism in response to shifting microenvironmental conditions can drive subpopulations of cells within colonies toward divergent behaviors. Understanding the interactions of these subpopulations-their potential for competition as well as cooperation-requires both a metabolic model capable of accounting for a wide range of environmental conditions, and a detailed dynamic description of the cells' shared extracellular space.

Results: Here we show that a cell's position within an in silico Escherichia coli colony grown on glucose minimal agar can drastically affect its metabolism: "pioneer" cells at the outer edge engage in rapid growth that expands the colony, while dormant cells in the interior separate two spatially distinct subpopulations linked by a cooperative form of acetate crossfeeding that has so far gone unnoticed.