Serum miRNA improves the accuracy of a multivariate index assay for triage of an adnexal mass.

Objective: To determine whether a multimodal assay combining serum microRNA with protein biomarkers and metadata improves triage assessment of an adnexal mass.

Methods: Serum samples from 468 training subjects (191 cancer cases and 277 benign adnexal mass controls or healthy controls) were analyzed for seven protein biomarkers and 180 miRNA. Circulating analyte data were combined with age and menopausal status (metadata) into a neural network model to classify samples as cases or controls.

Ovarian Cancer surgical consideration is markedly improved by the neural network powered-MIA3G multivariate index assay.

Background: Surgery remains the main treatment option for an adnexal mass suspicious of ovarian cancer. The malignancy rate is, however, only 10-15% in women undergoing surgery. This results in a high number of unnecessary surgeries.

Neural network-derived multivariate index assay demonstrates effective clinical performance in longitudinal monitoring of ovarian cancer risk.

Objective: We recently characterized the clinical performance of a multivariate index assay (MIA3G) to assess ovarian cancer risk for adnexal masses at initial presentation. This study evaluated how MIA3G varies when applied longitudinally to monitor risk during clinical follow-up.

Method: The study evaluated women presenting with adnexal masses from eleven centers across the US.

Validation of a deep neural network-based algorithm supporting clinical management of adnexal mass.

Background: Conservative management of adnexal mass is warranted when there is imaging-based and clinical evidence of benign characteristics. Malignancy risk is, however, a concern due to the mortality rate of ovarian cancer. Malignancy occurs in 10-15% of adnexal masses that go to surgery, whereas the rate of malignancy is much lower in masses clinically characterized as benign or indeterminate.

Low-risk multivariate index assay scores, physician referral and surgical choices in women with adnexal masses.

Objective: To assess the use of Multivariate Index Assay (MIA OVA1) by gynecologists and determine referral practices and surgical decision making for women with adnexal masses and low-risk MIA OVA1 scores.

Methods: Information on patients who received an OVA1 test was collected retrospectively from 22 gynecologic practices through a chart review. Referral patterns were examined for patients with low-risk OVA1 results prior to first surgical intervention.

Tyrosine Kinase Inhibitors Reduce NMDA NR1 Subunit Expression, Nuclear Translocation, and Behavioral Pain Measures in Experimental Arthritis.

In the lumbar spinal cord dorsal horn, release of afferent nerve glutamate activates the neurons that relay information about injury pain. Here, we examined the effects of protein tyrosine kinase (PTK) inhibition on NMDA receptor NR1 subunit protein expression and subcellular localization in an acute experimental arthritis model. PTK inhibitors genistein and lavendustin A reduced cellular histological translocation of NMDA NR1 in the spinal cord occurring after the inflammatory insult and the nociceptive behavioral responses to heat.

Clinical Performance Comparison of Two In-Vitro Diagnostic Multivariate Index Assays (IVDMIAs) for Presurgical Assessment for Ovarian Cancer Risk.

Introduction: Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, especially for ovarian cancer. Proper identification prior to surgery would permit appropriate referral to a specialty center in cases likely to be ovarian cancer, as optimal outcomes in such cases are obtained when surgical staging and treatment are provided at the time of initial surgery.

Methods: We compared the screening capabilities of two in vitro diagnostic multivariate index assays (IVDMIAs), a new IVDMIA (second-generation multivariate index assay: MIA2G) and a currently used triage algorithm (Risk of Ovarian Malignancy Assay: ROMA).

Combined symptom index and second-generation multivariate biomarker test for prediction of ovarian cancer in patients with an adnexal mass.

Objective: To assess the performance of a symptom index (SI) and multivariate biomarker panel in the identification of ovarian cancer in women presenting for surgery with an adnexal mass.

Study Design: Prospective study of patients seen at a tertiary medical center. Following consent, patients completed an SI and preoperative serum was collected for individual markers (CA 125) and a second-generation FDA-cleared biomarker test (MIA2G).

Validation of a second-generation multivariate index assay for malignancy risk of adnexal masses.

Background: Women with adnexal mass suspected of ovarian malignancy are likely to benefit from consultation with a gynecologic oncologist, but imaging and biomarker tools to ensure this referral show low sensitivity and may miss cancer at critical stages.

Objective: The multivariate index assay (MIA) was designed to improve the detection of ovarian cancer among women undergoing surgery for a pelvic mass. To improve the prediction of benign masses, we undertook the redesign and validation of a second-generation MIA (MIA2G).

Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo.

The goal of this study was to enhance gene delivery and tumor cell transfection in vivo by using a combination of ultrasonication with complex nanoparticles consisting of two types of nanoparticles: PEI/DNA beta-gal plasmid with highly positive zeta-potential and air-filled poly (lactic-co-glycolic acid) (PLGA) particles (with negative zeta-potential) manufactured in our laboratory. The PLGA/PEI/DNA nanoparticles were a colloid with positive zeta-potential and injected i.v.

Applying small RNA molecules to the directed treatment of human diseases: realizing the potential.

Small interfering RNAs (siRNA) and microRNAs (miRNA) are gaining considerable attention in the pharmaceutical and biotechnology industries, as research has revealed their likely clinical and agricultural applications. The capacity of siRNAs to dramatically and specifically reduce the expression of targeted genes has spawned multiple clinical trials to establish the therapeutic potential of small RNAs targeting viral, cancer and other disease-related genes. The successful application of siRNAs will enable the development of therapeutic applications based on miRNAs that have been observed to contribute to a variety of human diseases.

Nanoscale engineering of a cellular interface with semiconductor nanoparticle films for photoelectric stimulation of neurons.

The remarkable optical and electrical properties of nanostructured materials are considered now as a source for a variety of biomaterials, biosensing, and cell interface applications. In this study, we report the first example of hybrid bionanodevice where absorption of light by thin films of quantum confined semiconductor nanoparticles of HgTe produced by the layer-by-layer assembly stimulate adherent neural cells via a sequence of photochemical and charge-transfer reactions. We also demonstrate an example of nanoscale engineering of the material driven by biological functionalities.

Whole-body hyperthermia induces up-regulation of vascular endothelial growth factor accompanied by neovascularization in cardiac tissue.

Whole-body hyperthermia (WBH) promotes cardiac protection against ischemia/reperfusion injury, in part by up-regulation of heat shock proteins (HSP). Whether heat stress also promotes up-regulation of angiogenic factors or induces endothelial cell proliferation is unknown. We studied the effects of heat stress on up-regulation of vascular endothelial growth factor (VEGF) and growth of new blood vessels following WBH.

Biocompatibility of native and functionalized single-walled carbon nanotubes for neuronal interface.

Single-walled carbon nanotubes (SWNTs) have unique mechanical, electrical, and optical properties and can be easily chemically modified; features that make them excellent candidate materials for applications as sensors and stimulators in neuronal tissue engineering. The purpose of this study was to demonstrate that SWNTs can support neuronal attachment and growth, that simple chemical modifications can be employed to control cell growth, that SWNTs do not interfere with ongoing neuronal function, and that neurons can be electrically coupled to SWNTs. Growth and attachment of the neuroblastoma*glioma NG108, a model neuronal cell, was assessed on unmodified SWNT substrates or substrates from SWNTs modified with 4-benzoic acid or 4-tert-butylphenyl functional groups using a simple functionalization method.

Unique temperature-activated neurons from pit viper thermosensors.

Rattlesnakes, copperheads, and other pit vipers have highly sensitive heat detectors known as pit organs, which are used to sense and strike at prey. However, it is not currently known how temperature change triggers cellular and molecular events that activate neurons supplying the pit organ. We dissociated and cultured neurons from the trigeminal ganglia (TG) innervating the pit organs of the Western Diamondback rattlesnake (Crotalus atrox) and the copperhead (Agkistrodon contortix) to investigate electrophysiological responses to thermal stimuli.

Tumour necrosis factor-alpha- vs. growth factor deprivation-promoted cell death: different receptor requirements for mediating nerve growth factor-promoted rescue.

Physiological and pathological aging of the central nervous system (CNS) is characterized by functional neuronal impairments which may lead to perturbed cell homeostasis and eventually to neuronal death. Many toxic events may underlie age-related neurodegeneration. These include the effects of beta amyloid, Tau and mutated presenilin proteins, free radicals and oxidative stress, pro-inflammatory cytokines and lack of growth factor support, which can be individually or collectively involved.

Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages.

Macrophages and CD4(+) lymphocytes are the principal target cells for human immunodeficiency virus type 1 (HIV-1) infection, but the molecular details of infection may differ between these cell types. During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63. Pretreatment of primary macrophages with anti-CD63 MAb, but not MAbs to other macrophage cell surface tetraspanins (CD9, CD81, and CD82), was shown to inhibit infection by several R5 and dualtropic strains, but not by X4 isolates.