Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to Acute Myocardial Infarction.

Herein, we have developed a drug-loaded matrix metalloproteinase (MMP)-responsive micellar nanoparticle (NP) intended for minimally invasive intravenous injection during the acute phase of myocardial infarction (MI) and prolonged retention in the heart for small-molecule drug delivery. Peptide-polymer amphiphiles (PPAs) bearing a small-molecule MMP inhibitor (MMPi), PD166793, were synthesized via ring-opening metathesis polymerization (ROMP) and formulated into spherical micelles by transitioning to aqueous solution. The resulting micellar NPs underwent MMP-induced aggregation, demonstrating enzyme responsiveness.

Inflammation-Responsive Micellar Nanoparticles from Degradable Polyphosphoramidates for Targeted Delivery to Myocardial Infarction.

Nanoparticles that undergo a localized morphology change to target areas of inflammation have been previously developed but are limited by their lack of biodegradability. In this paper, we describe a low-ring-strain cyclic olefin monomer, 1,3-dimethyl-2-phenoxy-1,3,4,7-tetrahydro-1,3,2-diazaphosphepine 2-oxide (MePTDO), that rapidly polymerizes via ring-opening metathesis polymerization at room temperature to generate well-defined degradable polyphosphoramidates with high monomer conversion (>84%). Efficient MePTDO copolymerizations with norbornene-based monomers are demonstrated, including a norbornenyl monomer functionalized with a peptide substrate for inflammation-associated matrix metalloproteinases (MMPs).

Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues.

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d.

Characterization of a mGluR5 Knockout Rat Model with Hallmarks of Fragile X Syndrome.

The number of reported cases of neurodevelopmental disorders has increased significantly in the last few decades, but the etiology of these diseases remains poorly understood. There is evidence of a fundamental link between genetic abnormalities and symptoms of autism spectrum disorders (ASDs), and the most common monogenetic inheritable form of ASDs is Fragile X Syndrome (FXS). Previous studies indicate that FXS is linked to glutamate signaling regulation by the G-protein-coupled metabotropic glutamate receptor 5 (mGluR5), which has been shown to have a regulatory role in neuroinflammation.

Targeted nanoscale therapeutics for myocardial infarction.

Nanoscale therapeutics have promise for the administration of therapeutic small molecules and biologics to the heart following myocardial infarction. Directed delivery to the infarcted region of the heart using minimally invasive routes is critical to this promise. In this review, we will discuss the advances and design considerations for two nanoscale therapeutics engineered to target the infarcted heart, nanoparticles and adeno-associated viruses.

Diffuse reflectance spectroscopy can differentiate high grade and low grade prostatic carcinoma.

Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients.

Anterior tumors of the prostate: diagnosis and significance.

Introduction: Prostate biopsies are usually taken from the peripheral rather than anterior region of the prostate. Consequently, tumors originating from the anterior apical region and transition zones may be under-sampled. We examined whether addition of transrectal anterior biopsy (TAB) would improve efficacy of prostate biopsies.

Optimization of prostate cancer diagnosis by increasing the number of core biopsies based on gland volume.

In this prospective, non-randomized phase-I clinical trial, we comparatively studied the performance of six laterally-directed biopsies or the modified fan-shaped biopsies (MFSB), midline sextant biopsies (MB), and transition zone biopsies (TZB) and examine their prostate cancer (PCa) detection rates. A total of 114 patients received combinations of MFSB, MB, and TZB based on prostate gland volume: those ≤15 cc received 8 biopsies; those >15 cc but ≤ 50 cc received 14 biopsies; and those >50 cc received 20 biopsies. The mean prostate-specific antigen (PSA) level, Gleason score, and prostate volume were 8.

Proliferative tumor doubling times of prostatic carcinoma.

Prostate cancer (PCa) has a variable biology ranging from latent cancer to extremely aggressive tumors. Proliferative activities of cancers may indicate their biological potential. A flow cytometric assay to calculate maximum proliferative doubling times (T(max)) of PCa in radical prostatectomy specimens after preoperative in vivo bromodeoxyuridine (BrdU) infusion is presented.

The metabolites citrate, myo-inositol, and spermine are potential age-independent markers of prostate cancer in human expressed prostatic secretions.

Objectives: Due to specific physiological functions, prostatic tissues and fluids have unique metabolic profiles. In this study, proton nuclear magnetic resonance spectroscopy ((1)H-NMRS) is used to assess potential metabolic markers of prostate cancer (PCa) in human expressed prostatic secretions (EPS).

Methods: Metabolic profiles of EPS from 52 men with PCa and from 26 healthy controls were analyzed using quantitative (1)H-NMRS.

Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.

Objective: To identify the precise location of prostate cancer within the gland and thus possibly permit more aggressive therapy of the lesion, while potentially sparing the noncancerous gland from ablative therapy.

Materials And Methods: Three-dimensional "solid" computer models were reconstructed for 86 autopsy specimens and 20 stage T1c radical prostatectomy specimens. Transperineal biopsies were simulated for grid sizes of 5-mm (method A) and 10-mm (method B) with an 18 G, 23-mm long biopsy needle.

Sulindac metabolites induce caspase- and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells.

Colorectal cancer (CRC) is the second leading cause of cancer death in the USA. Accumulation of beta-catenin protein is nearly ubiquitous in colon adenomas and cancers, presumably due to mutations in the APC or beta-catenin genes that inhibit proteasome-dependent degradation of beta-catenin protein. Substantial clinical, epidemiological, and animal evidence indicate that sulindac and other non-steroidal anti-inflammatory drugs (NSAIDs) prevent the development of CRC.