Tumor-specific intracellular delivery: peptide-guided transport of a catalytic toxin.

There continues to be a need for cancer-specific ligands that can deliver a wide variety of therapeutic cargos. Ligands demonstrating both tumor-specificity and the ability to mediate efficient cellular uptake of a therapeutic are critical to expand targeted therapies. We previously reported the selection of a peptide from a peptide library using a non-small cell lung cancer (NSCLC) cell line as the target.

Introduction of plasmid encoding for rare tRNAs reduces amplification bias in phage display biopanning.

Amplification bias is a major hurdle in phage display protocols because it imparts additional, unintended selection pressure beyond binding to the desired target. One potential source of amplification bias is the inherent lack of codon optimization that occurs within phage display libraries. Here we present a method that reduces amplification bias by addition of a plasmid that encodes six low abundance tRNAs into K91 Escherichia coli.

Dimerization of a phage-display selected peptide for imaging of αvβ6- integrin: two approaches to the multivalent effect.

The integrin αvβ6 is an emerging biomarker for non-small cell lung cancer (NSCLC). An αvβ6-binding peptide was previously selected from a phage-displayed peptide library. Here, we utilize a multivalent design to develop a peptidic probe for positron emission tomography (PET) imaging of αvβ6+ NSCLC tumors.

Identification and characterization of a suite of tumor targeting peptides for non-small cell lung cancer.

Tumor targeting ligands are emerging components in cancer therapies. Widespread use of targeted therapies and molecular imaging is dependent on increasing the number of high affinity, tumor-specific ligands. Towards this goal, we biopanned three phage-displayed peptide libraries on a series of well-defined human non-small cell lung cancer (NSCLC) cell lines, isolating 11 novel peptides.

A liposomal drug platform overrides peptide ligand targeting to a cancer biomarker, irrespective of ligand affinity or density.

One method for improving cancer treatment is the use of nanoparticle drugs functionalized with targeting ligands that recognize receptors expressed selectively by tumor cells. In theory such targeting ligands should specifically deliver the nanoparticle drug to the tumor, increasing drug concentration in the tumor and delivering the drug to its site of action within the tumor tissue. However, the leaky vasculature of tumors combined with a poor lymphatic system allows the passive accumulation, and subsequent retention, of nanosized materials in tumors.

Novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (Orf virus) genome.

Background: The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach.

Results: The genome of Parapoxvirus ovis (Orf virus) was sequenced, annotated, and then used to PCR-amplify its open-reading-frames.

Synthesis and biological evaluation of a peptide-paclitaxel conjugate which targets the integrin αvβ₆.

The integrin α(v)β(6) is an emergent biomarker for non-small cell lung cancer (NSCLC) as well as other carcinomas. We previously developed a tetrameric peptide, referred to as H2009.1, which binds α(v)β(6) and displays minimal affinity for other RGD-binding integrins.

Synthesis and characterization of a high-affinity {alpha}v{beta}6-specific ligand for in vitro and in vivo applications.

The α(v)β(6) integrin is an attractive therapeutic target for several cancers due to its role in metastasis and its negligible expression in normal tissues. We previously identified a peptide from a phage-displayed peptide library that binds specifically to α(v)β(6). The tetrameric version of the peptide has higher affinity for its cellular targets than the corresponding monomers.

Biopanning of phage displayed peptide libraries for the isolation of cell-specific ligands.

One limitation in the development of biosensors for the early detection of disease is the availability of high specificity and affinity ligands for biomarkers that are indicative of a pathogenic process. Within the past 10 years, biopanning of phage displayed peptide libraries on intact cells has proven to be a successful route to the identification of cell-specific ligands. The peptides selected from these combinatorial libraries are often able to distinguish between diseased cells and their normal counterparts as well as cells in different activation states.

Peptide-targeted polyglutamic acid doxorubicin conjugates for the treatment of alpha(v)beta(6)-positive cancers.

Most chemotherapeutics exert their effects on tumor cells as well as their healthy counterparts, resulting in dose limiting side effects. Cell-specific delivery of therapeutics can increase the therapeutic window for treatment by maintaining the therapeutic efficacy while decreasing the untoward side effects. We have previously identified a peptide, named H2009.

Advances in molecular imaging of pancreatic beta cells.

The development of non-invasive imaging methods for early diagnosis of beta cell associated metabolic diseases, including type 1 and type 2 diabetes (T1D and T2D), has recently drawn interest from the molecular imaging community and clinical investigators. Due to the challenges imposed by the location of the pancreas, the sparsely dispersed beta cell population within the pancreas, and the poor understanding of the pathogenesis of the diseases, clinical diagnosis of beta cell abnormalities is still limited. Current diagnostic methods are invasive, often inaccurate, and usually performed post-onset of the disease.

Measures of homophobia among nursing students and faculty: a Midwestern perspective.

It is well documented that homophobia exists among healthcare providers including nurses. However, little research is available on the level of homophobia among nursing students and nursing faculty. Using the Index of Attitudes Toward Homosexuals (IAH) and the Homophobic Behavior of Students Scale (HBSS) 241 nursing students and 32 faculty in a Midwest university were invited to participate.

A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer.

The development of new modes of diagnosis and targeted therapy for lung cancer is dependent on the identification of unique cell surface features on cancer cells and isolation of reagents that bind with high affinity and specificity to these biomarkers. We recently isolated a 20-mer peptide which binds to the lung adenocarcinoma cell line, H2009, from a phage-displayed peptide library. We show here that the cellular receptor for this peptide, TP H2009.

2004 National Atrazine Occurrence Monitoring Program using the Abraxis ELISA method.

The goal of this project was to gain a better understanding of atrazine occurrence in the United States by surveying drinking water utilities' sources and finished water for atrazine on a weekly basis for seven months. Atrazine is a contaminant of interest because the United States Environmental Protection Agency (USEPA) has found short-term atrazine exposure above the drinking water maximum contaminant level (MCL) to potentially cause heart, lung, and kidney congestion, low blood pressure, muscle spasms, weight loss, and damage to the adrenal glands. Long-term exposure to atrazine concentrations above the drinking water MCL has been linked to weight loss, cardiovascular damage, retinal and muscle degeneration, and cancer.

Novel ligands for cancer diagnosis: selection of peptide ligands for identification and isolation of B-cell lymphomas.

Objective: Lymphoma and leukemia account for nearly 8% of cancer fatalities each year. Present treatments do not differentiate between normal and malignant cells. New reagents that distinguish malignant cells and enable the isolation of these cells from the normal background will enhance the molecular characterization of disease and specificity of treatment.

Can a single-reference approach provide a balanced description of ground and excited states? A comparison of the completely renormalized equation-of-motion coupled-cluster method with multireference quasidegenerate perturbation theory near a conical intersection and along a photodissociation coordinate in ammonia.

We calculated the two lowest electronically adiabatic potential energy surfaces of ammonia in the region of the conical intersection and at a sequence of geometries along which one of the N-H bonds is broken. We employed both a multireference (MR) method and a single-reference (SR) method. The MR calculations are based on multiconfiguration quasidegenerate perturbation theory (MC-QDPT) with a 6-311+G(3df,3pd) basis set.

Hexavalent chromium removal by reduction with ferrous sulfate, coagulation, and filtration: a pilot-scale study.

A flow-through pilot-scale system was tested for removal of Cr(VI) from contaminated groundwater in Glendale, California. The process consisted of the reduction of Cr(VI) to Cr(lll) using ferrous sulfate followed by coagulation and filtration. Results indicated that the technology could reduce influent Cr(VI) concentrations of 100 microg L(-1) to below detectable levels and also remove total Cr (Cr(VI) plus Cr(lll)) to very low concentrations (< 5 microg L(-1)) under optimized conditions.

Peptide-mediated targeting of the islets of Langerhans.

Strategies for restoring beta-cell function in diabetic patients would be greatly aided by the ability to target genes, proteins, or small molecules specifically to these cells. Furthermore, the ability to direct imaging agents specifically to beta-cells would facilitate diagnosis and monitoring of disease progression. To isolate ligands that can home to beta-cells in vivo, we have panned a random phage-displayed 20-mer peptide library on freshly isolated rat islets.

Balancing dynamic and nondynamic correlation for diradical and aromatic transition states: a renormalized coupled-cluster study of the cope rearrangement of 1,5-hexadiene.

Single-reference coupled-cluster calculations employing the completely renormalized CCSD(T) (CR-CCSD(T)) approach have been used to examine the mechanism of the Cope rearrangement of 1,5-hexadiene. In agreement with multireference perturbation theory, the CR-CCSD(T) method favors the concerted mechanism of the Cope rearrangement involving an aromatic transition state. The CCSD(T) approach, which is often regarded as the "gold standard" of electronic structure theory, seems to fail in this case, favoring pathways through diradical structures.

A library-selected, Langerhans cell-targeting peptide enhances an immune response.

The ability to deliver antigens and immunomodulators specifically to Langerhans cells (LCs) in the skin could impact vaccine development. However, cell-specific targeting of therapeutic molecules remains a challenge in biomedicine. Using phage display technologies, we have developed a protocol that identifies peptides that mediate uptake into target cell types.

Cell-specific delivery of a chemotherapeutic to lung cancer cells.

We report that lung cancer-targeting peptides isolated from a peptide library can be used to deliver an active chemotherapeutic in a cell-specific fashion. The peptides were removed from the context of the phage and placed on a pegylated tetrameric scaffold. The tetrameric peptides were shown to block uptake of their cognate phage.

In vitro selection of a peptide with high selectivity for cardiomyocytes in vivo.

One approach to targeted therapies for cardiovascular disease relies on isolating ligands that enhance the tissue-specific uptake of genes or drugs by heart cells. To obtain heart-targeting ligands, phage display biopanning was used to isolate a 20-mer peptide that binds to isolated primary cardiomyocytes. The isolated phage, PCM.

Genetic immunization: what's in a name?

The concept and demonstration of genetic immunization (GI) was first introduced in 1992. At the time it appeared to be a revolutionary new approach in vaccinology. Since then, genetic immunization has been applied with much success in a wide variety of model and natural systems.