Matching Items (49)

133582-Thumbnail Image.png

Adapting Laser Activated Sutures for Intestinal Surgeries

Description

Current wound closure technology is limited, and lacks key elements \u2014 such as the formation of an immediate seal \u2014 that could otherwise resolve some of the common and life threatening complications associated with certain surgeries. Previous research has produced

Current wound closure technology is limited, and lacks key elements \u2014 such as the formation of an immediate seal \u2014 that could otherwise resolve some of the common and life threatening complications associated with certain surgeries. Previous research has produced nanosealants capable of providing that immediate seal through the use of laser activation with a near infrared laser. Here, we have developed a biocompatible suture utilizes the same mechanics to provide the tensile strength needed to replace or supplement existing suture lines. Laser activated tissue integrating sutures (LATIS), are shown to have 75% of the tensile strength of commercially available PGA sutures, while still exhibiting the same laser mediated localized heating effect at power densities of as low as 1.6 W/cm2. LATIS has been shown to reach the temperature ranges needed for protein interdigitation, but suffers from low wet mechanical strength. Preparatory steps or solvents for chemical crosslinking generally dehydrate LATIS sutures, causing a shriveling effect that weakens the overall mechanical strength of the suture. To resolve this, a new method of drying, by which LATIS sutures are dried under tension on a suspended platform, has been shown to decrease control suture strength, but restore the strength of chemically treated LATIS sutures to the level of control sutures or above. These promising results suggest that follow-up work with chemical cross-linkers may produce the increases in LATIS wet strength that are needed for its implementation in deeper tissue surgeries.

Contributors

Agent

Created

Date Created
2018-05

134426-Thumbnail Image.png

Lipopolymer-Mediated Transgene Delivery to Human Stem Cells

Description

Genetic manipulation of human cell lines has widespread applications in biomedical research ranging from disease modeling to therapeutic development. Human cells are generally difficult to genetically engineer, but exogenous nucleic acids can be expressed by viral, chemical, or nonchemical means.

Genetic manipulation of human cell lines has widespread applications in biomedical research ranging from disease modeling to therapeutic development. Human cells are generally difficult to genetically engineer, but exogenous nucleic acids can be expressed by viral, chemical, or nonchemical means. Chemical transfections are simpler in practice than both viral and nonchemical delivery of genetic material, but often suffer from cytotoxicity and low efficiency. Novel aminoglycoside antibiotic-derived lipopolymers have been synthesized to mediate transgene delivery to human cells. These polymers are comprised of either paromomycin or apramycin crosslinked with glycerol diglycidylether and derivatized with stearoyl chloride in varying molar ratios. In this work, three previously identified target lipopolymers were screened against a library of human embryonic and induced pluripotent stem cell lines. Cells were transfected with a plasmid encoding green fluorescent protein (GFP) and expression was quantified with flow cytometry 48 hours after transfection. Transfection efficiency was evaluated between three distinct lipopolymers and four lipopolymer:DNA mass ratios. GFP expression was compared to that of cells transfected with commercially available chemical gene delivery reagent controls\u2014JetPEI, Lipofectamine, and Fugene\u2014at their recommended reagent:DNA ratios. Improved transgene expression in stem cell lines allows for improved research methods. Human stem cell-derived neurons that have been genetically manipulated to express phenotypic characteristics of aging can be utilized to model neurodegenerative diseases, elucidating information about these diseases that would be inaccessible in unmanipulated tissue.

Contributors

Agent

Created

Date Created
2017-05

134534-Thumbnail Image.png

Amino Acid Templated Gold Nanoparticles as Sensors of Ionizing Radiation

Description

This research addresses the need for improvement in radiation sensors for applications of ionizing radiation such as radiotherapy. The current sensors involved are polymer gel dosimeters, MOSFETs, radio-chromic films, etc. Most of the sensors involved require expensive equipment's and processing

This research addresses the need for improvement in radiation sensors for applications of ionizing radiation such as radiotherapy. The current sensors involved are polymer gel dosimeters, MOSFETs, radio-chromic films, etc. Most of the sensors involved require expensive equipment's and processing facilities for readout. There is still a need to develop better sensors that can be clinically applied. There are numerous groups around the world trying to conceive a better dosimeter. One of the radiation sensors that was developed recently was based on fluorescence signal emitted from the sensor. To advance the field of radiation sensors, a visual indicator has been developed in-lab as a method of detect ionizing radiation. The intensity of change in color is directly dependent on the amount of incident ionizing radiation. An aqueous gold nanoparticle sensor can be used to accurately determine the incident amount of ionizing radiation1. A gold nanoparticle sensor has been developed in lab with the use of hexadecyltrimethylammonium bromide (C16TAB) as the templating molecule. In the presence of ionizing radiation, the colorless gold salt is reduced and templated, creating a dispersion within the fluid1. The formation of suspended nanoparticles leads to a color change that can be visually detected and accurately analyzed through the employment of a spectrometer. Unfortunately, the toxicity of C16TAB is high. It is expected the toxicity can be reduced by replacing C16TAB with an amino acid, as amino acids can act as templating molecules in the solution and many are naturally occuring2. The experiments included a screening of 20 natural amino acids and 12 unnatural amino acids with the gold salt solution in the presence of ionizing radiation. Stability and absorbance testing was conducted on the amino acid sensors. Additional screening of lead amino acid sensors at various concentrations of irradiation was conducted.

Contributors

Agent

Created

Date Created
2017-05

128357-Thumbnail Image.png

Emerging Applications of Exosomes in Cancer Therapeutics and Diagnostics

Description

Exosomes are nanoscale extracellular vesicles that are shed from different cells in the body. Exosomes encapsulate several biomolecules including lipids, proteins, and nucleic acids, and can therefore play a key role in cellular communication. These vesicles can be isolated from

Exosomes are nanoscale extracellular vesicles that are shed from different cells in the body. Exosomes encapsulate several biomolecules including lipids, proteins, and nucleic acids, and can therefore play a key role in cellular communication. These vesicles can be isolated from different body fluids and their small sizes make them attractive in various biomedical applications. Here, we review state-of-the art approaches in exosome isolation and purification, and describe their potential use in cancer vaccines, drug delivery, and diagnostics.

Contributors

Created

Date Created
2017-03

128991-Thumbnail Image.png

Parallel Screening of FDA-Approved Antineoplastic Drugs for Identifying Sensitizers of TRAIL-Induced Apoptosis in Cancer Cells

Description

Background: Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating

Background: Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis.

Methods: FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis.

Results: Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells.

Conclusions: The identification of a number of FDA-approved drugs as TRAIL sensitizers can expand chemotherapeutic options for combination treatments in prostate and pancreatic cancer diseases.

Contributors

Agent

Created

Date Created
2011-11-01

136370-Thumbnail Image.png

COMBINATORIAL SYNTHESIS OF INTRINSICALLY PHOTOLUMINESCENT POLY(AMINO ETHER)S AND THERMOSET RESINS

Description

Increased investigation into the development of macromolecular fluorophores has resulted in the synthesis and discovery of several potential candidates. These include modified and polymeric based dendritic structures, hyperbranched polymers and linear polymers. Strong inherent blue photoluminescence has been recently described

Increased investigation into the development of macromolecular fluorophores has resulted in the synthesis and discovery of several potential candidates. These include modified and polymeric based dendritic structures, hyperbranched polymers and linear polymers. Strong inherent blue photoluminescence has been recently described in linear polyamine polymers in the absence of any chemical modifications. Here we describe the screening of amine/polyamine compounds for inherent photoluminescence. Several compounds that exhibited strong inherent blue photoluminescence following excitation with UV light were identified. Furthermore we demonstrated successful synthesis of poly(amino ether) polymers as well as chemically cross-linked poly(amino ether) thermosets with the lead Pentaethylenehexamine which was found to have strong inherent blue photoluminescence. The polymers and thermosets were found to retain the photoluminescent properties of the original lead compound. The polymers and thermosets were investigated for their ability to sequester heavy metals from aqueous solutions. An increased decrease in initial photoluminescence was observed as the materials were incubated with increasing metal salt concentration as a result of metal binding sequestration. The poly(amino ether) polymers were found to have higher sensitivity for metal sequestration when compared to equivalent amount of linear 25 kDa polyethylenimine. The strong inherent blue photoluminescence and the ease of synthesis of the poly(amino ether) polymers and thermosets give these materials strong potential for future applications as sensors.

Contributors

Agent

Created

Date Created
2015-05

135646-Thumbnail Image.png

Investigation of Cell Media and Aminoglycoside Hydrogel Properties for Cancer Cell Dormancy

Description

In a dormant state, cancer cells survive chemotherapy leaving the opportunity for cancer cell relapse and metastasis ultimately leading to patient death. A novel aminoglycoside-based hydrogel ‘Amikagel’ developed in Dr. Rege’s lab serves as a platform for a 3D tumor

In a dormant state, cancer cells survive chemotherapy leaving the opportunity for cancer cell relapse and metastasis ultimately leading to patient death. A novel aminoglycoside-based hydrogel ‘Amikagel’ developed in Dr. Rege’s lab serves as a platform for a 3D tumor microenvironment (3DTM) mimicking cancer cell dormancy and relapse. Six Amikagels of varying mechanical stiffness and adhesivities were synthesized and evaluated as platforms for 3DTM formation through cell viability and cell cycle arrest analyses. The impact of fetal bovine serum concentration and bovine serum albumin concentration in the media were studied for their impact on 3DTM formation. These experiments allow us to identify the best possible Amikagel formulation for 3DTM.

Contributors

Agent

Created

Date Created
2016-05

135544-Thumbnail Image.png

Anti-Neoplastic Drug Conjugated Aminoglycoside Microbeads for Plasmid DNA Binding

Description

Plasmid DNA (pDNA) purification has been extensively investigated for various biological and biochemical applications such as transfection, polymerase chain reaction and DNA therapeutics. In the previous paper, we have described the synthesis, characterization and evaluation of microbeads (“Amikabeads”) derived from

Plasmid DNA (pDNA) purification has been extensively investigated for various biological and biochemical applications such as transfection, polymerase chain reaction and DNA therapeutics. In the previous paper, we have described the synthesis, characterization and evaluation of microbeads (“Amikabeads”) derived from aminoglycoside amikacin for pDNA binding via anion-exchange chromatography. Here, we investigated the pDNA binding performance of conjugating Amikabeads with two highly specific DNA binding ligands via minor groove hydrophobic interaction. The pDNA maximum binding capacity of doxorubicin drug-conjugated Amikabeads (“doxo-beads”) was found out to be 429 μg pDNA/ mg of doxo-beads with a Langmuir constant of 8.21*10-4 L/mg, whereas the binding performance of berenil drug-conjugated "mikabeads (“berenil-beads”) was 142 μg pDNA/mg of berenil-beads with a adsorption constant of 4.71*10-5 L/mg. In addition, the desorption percentage of doxo-beads and berenil-beads was obtained as 52% and 41%, respectively. Our results indicate that by conjugating with highly specific DNA binding ligands, Amikabeads-drug complex enhances the pDNA binding performance and contains a promising potential for future applications in biotechnology field.

Contributors

Agent

Created

Date Created
2016-05

136570-Thumbnail Image.png

Characterizing the activity of alcohol dehydrogenase from Lactobacillus brevis on primary and secondary alcohol biofuel precursors

Description

The R-specific alcohol dehydrogenase (RADH or LVIS_0347) from Lactobacillus brevis LB19 was found to possess activity on several short chain aldehydes and ketones. This broad substrate specificity was previously uncharacterized. To demonstrate its relevance to the biofuels industry as well

The R-specific alcohol dehydrogenase (RADH or LVIS_0347) from Lactobacillus brevis LB19 was found to possess activity on several short chain aldehydes and ketones. This broad substrate specificity was previously uncharacterized. To demonstrate its relevance to the biofuels industry as well as its broader utility for chiral reductions, a detailed characterization was performed to further investigate the activity and function of RADH.

Contributors

Agent

Created

Date Created
2015-05

136053-Thumbnail Image.png

Molecular Engineering of Novel Polymeric Agents for Targeted Cancer Gene Therapy

Description

Abstract Molecular Engineering of Novel Polymeric Agents for Targeted Cancer Gene Therapy Dana Matthews Cancer gene cell therapy is a strategy that involves the administration of genes for correcting the effect of mutated cancer cells in order to induce tumor

Abstract Molecular Engineering of Novel Polymeric Agents for Targeted Cancer Gene Therapy Dana Matthews Cancer gene cell therapy is a strategy that involves the administration of genes for correcting the effect of mutated cancer cells in order to induce tumor cell death. In particular, genes that encode for pro-apoptotic proteins can result in death of tumor cells. Prostate cancer is a very common cancer among males in America, and as highly destructive chemotherapy and radiation are generally the only treatments available once the cancer has metastasized, there is a need for the development of treatments that can specifically target and kill prostate cancer cells, while demonstrating low toxicity to other tissue. This experiment will attempt to create such a treatment through gene therapy techniques. The parallel synthesis and DNA binding affinity assay utilized in these experiments have produced a polymer that surpasses pEI-25, a gene delivery polymer standard, in both transfection efficacy and low cytotoxicity and trafficking of polyplexes in the cell, and finding methods to increase the transfection efficacy and specificity of polyplexes for PC3-PSMA cells.

Contributors

Agent

Created

Date Created
2008-12