Category Archives: Medicine

Simple, cost-effective, flexible system for micro/nano particle manipulation

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Summary:

The availability of mobile magnetic traps offers new control needed for rapid progress at the frontiers of several branches of science and engineering. Ohio State researchers have discovered a way to create tunable mobile traps along a nanowire, which allows the manipulation and movement of nanoparticles along the wire. The femto- to pico-Newton scale forces possible with this method, which are delivered using electric currents, are ideally suited for probing single microparticles and biomolecules in the 10 nanometer to 100 micrometer length scales. Additionally, the nanoparticle(s) can be tethered to larger molecules, allowing manipulation of the larger molecules. As an example, a DNA strand could have each end attached to separate nanoparticles and then stretched as the nanoparticles are moved away from each other.

Potential Applications:

  • Clinical diagnosis
  • Biomolecule analysis
  • Forensics
  • Enviromental analysis
  • Nanofluidics

Advantages:

  • Easy to engineer magnetic domain
  • Simple and accurate manipulation of nanoparticles
  • Real-time observation of single or multiple objects trapped along the nanowire
  • Uses electric currents to transport along predetermined pathways
  • Two or more functionalized particles at the mobile traps can be linked to create a planar magnetic tweezer stage

Novel Peptide Vaccines and Active Immunization for Cancer Prevention and Therapy

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Summary:

Researchers at The Ohio State University have developed an active prophylactic/preventive human cancer vaccine for HER-2 expressing cancers. HER-2/neu is a unique oncoprotein that is over-expressed in a number of human tumors including breast, ovary, lung, stomach, endometrium and bladder, and is associated with markedly aggressive forms of cancer with a worse prognosis of several malignancies. Existing passive immunotherapeutic approaches require frequent treatments, have limited duration of action, produce undesired immunogenecity and incur significant risks of cardiotoxicities. The OSU technology may overcome many of these concerns by allowing the patient to produce their own antibodies to HER-2. The novel vaccine is now nearing completion of Phase I human clinical trials at OSU’s James Cancer Hospital. Results from advanced cancer patients (Stage IV) show no toxicity and several patients have had high immune responses to the vaccine. The peptide design platform on which this vaccine is based is highly extendable into therapeutics and other diseases:

  • Inhibiting tumor growth, invasion and metastasis: the inclusion of a VEGF inhibitor, a known contributor to angiogenesis, to the HER-2 vaccine can improve cancer treatment (status: preclinical evaluation).
  • Developing additional vaccines: the development of a novel vaccine for the treatment and prevention of epithelial ovarian cancer is underway (status: preclinical studies).
  • Identifying new approaches for disease treatment: new peptide therapeutics for autoimmune diseases can treat multiple sclerosis, rheumatoid arthritis, diabetes, lupus and allergies (status: preclinical testing).

The investment to date is:

  • HER-2/VEGF $4.5 million, $1.2 million pending
  • Autoimmune $600K

Currently, for the Cancer Vaccine and Therapeutics there are four patent families in prosecution and one US patent allowed. A US patent is pending for the autoimmune application.

Potential Applications:

Treatment and prevention of breast, ovarian, lung, stomach, endometrial and bladder cancers.

Advantages:

  • The patient produces the antibodies, reducing the amount and frequency of dosing
  • Significantly lower probability of toxicity compared to existing treatments.
  • Active immunization approach allows a patient to be treated before cancer is detected.

Therapeutic Peptides for Cardiovascular Disease

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Summary:

Peripheral blood contains a small subset of circulating bone marrow-derived cells termed endothelial progenitor cells, which represent a heterogeneous population with varying capacities to assume a differentiated and functional endothelium phenotype. Human blood outgrowth endothelial cells (HBEOC) isolated from this subset of cells express several endothelial markers and have high proliferative capacity. HBOECs have been implicated in myocardial repair after infarction, in the propagation of angiogenesis following ischemia, and in vascular repair after injury. A panel of novel peptide ligands have been developed that bind with high affinity and specificity to HBEOCs. HBEOC-specific ligands have the potential to serve as targeting agents for drug- or gene-delivery vehicles and diagnostic probes for non-invasive, high-resolution imaging. These peptides could also be immobilized on implant surfaces, such as prosthetic vascular grafts or stents, to harness the beneficial functions of endothelial progenitors to accelerate the healing process and promote biocompatibility.

Potential Applications:

  • Method of HBOEC specific drug- or gene-delivery
  • Use as targeting agents in diagnostic probes for non-invasive, high-resolution imaging
  • potential coating for implant surfaces for accelerated healing and increased biocompatibility
  • Valuable research tool for HBOEC cell purification and analysis

Undetectable, Unjammable, and Interference-Free Ultra Wideband Radar System

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Summary:

Researchers at the Ohio State University have developed a virtually undetectable ultra wide band radar system that transmits pseudo random noise. On receive, the radar system cross-correlates a copy (possibly modified) of the original waveform with the receive signals. If a target reflects the signal (with modifications) then the radar will detect the reflection, the time delay, and Doppler. Thus the radar can tell the distance to a reflecting object and its relative speed. This is done using a waveform that will not interfere with other users of the spectrum. The noise waveform is extremely hard to detect. Researchers have further developed a system of storing the waveforms and performing the cross correlation at a particular time delay using a single memory device and no delay devices. This lends to the creation of a small, low cost, low power, stealthy radar that cannot be easily detected by conventional radar detection equipment and can be used for very short range applications. The radar can also be used to identify radar targets by using a pair of waveforms matched to the target radar impulse response. Thus the radar can also be used to detect only specific types of targets, as maybe required by the application.

Potential Applications:

  • Speed radar gun manufacturers seeking an undetectable radar gun
  • Simple moving vehicle/person/object with identification potential (automotive lane change warning)
  • Highway management to evaluate strength of material, or helicopter air to air warning systems
  • Low cost ground penetration radar for pipes, land mine detection, or probing human bodies
  • Low cost building penetration radar (security systems at casinos and airports)
  • Cross section instrumentation radar with inverse synthetic aperture imaging radar ability
  • Moving Radar, synthetic aperture radar systems

Advantages:

  • Robust with reference to interference or jamming – thus undetectable and hard to intercept
  • Unlikely to interfere with other noise radar systems or other radar systems in the same band
  • Low cost, small, light weight, and can be used for very short-range applications
  • Can be trained to be target specific (with the ability to specify multiple targets)
  • Would require no license to operate in civilian bands, and is fully coherent in amplitude and phase

Non-blinking, Color-changing Quantum Dot Composite Nanoparticles

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Summary:

Quantum dots are fluorescent nanoparticles (<50 nm) with known applications including single molecule tracking, cell tracking, flow cytometry, and in vivo imaging.  A major challenge with the use of quantum dots in settings where a single quantum dot is conjugated to a single target for tracking purposes is blinking of the quantum dot.  Blinking is the result of the random switching of the fluorescence of the quantum dot from the on-state to the off-state.  This phenomenon is particularly problematic in tracking applications because the trajectories of the targets being tracked are broken.  In the past few years several designs of "non-blinking quantum dots" have been reported.  Blinking, however, is the best (and often the only feasible) in situ indicator of particle aggregation status in tracking studies.  The ability to make sure individual (or small aggregates of) molecules/particles rather than large aggregates are being tracked is crucial in tracking studies. 

Researchers at OSU have solved these two seemingly irreconcilable problems simultaneously by developing quantum dot composite nanoparticles with two key features: blinking-reduction and color-changing, the latter of which permits easy aggregation status evaluation in situ.  The strategy of producing quantum dots of multiple colors into a nanocontainer (micelle).  Because blinking dynamics of different quantum dots are out of phase, OSU’s composite nanoparticles emit uninterrupted color-changing fluorescence, with color-changing serving as the aggregation-status indicator. 

Continuous color-changing fluorescences of the Quantum Dot Composite Nanoparticles can provide scientists both the ability of imaging single (or small aggregates of) targets for long-term studies and the confidence of knowing that they are indeed imaging single (or small aggregates of) targets in tracking studies of biological processes.  Additional features of these novel fluorescent nanoparticles developed at OSU include ease of synthesis and bioconjugation, small size, high tolerance to biological environments, and ability to distinguish particle moving out-of-focus from blinking, which is another longstanding problem in quantum dot-based tracking.

Publications
Ruan, G. & Winter, J.O. Alternating-color quantum dot nanocomposites for particle tracking. Nano Letters (published on web Feb 15 2011).

Ruan, G. & Winter, J.O. Multi-color Nanoparticles for Single Particle Tracking.  American Institute of Chemical Engineers Annual Meeting, Salt Lake City 2010. 

Antagonist for Human Prolactin

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Summary:

Cancers of the breast and prostate are the second leading causes of cancer-related deaths among women and men, respectively. Together, these cancers were responsible for more than 360,000 new cases and 73,000 deaths in the U.S. during the year 2000. Few therapeutic compounds increase long-term survival or reduce morbidity. Human prolactin is a hormone produced by the pituitary gland and the placenta (among other tissues such as the breast and prostate). Receptors for this hormone are found in many tissues of the body including the breast and prostate. This hormone is important for lactation (breast milk production) and normal prostate development. However, prolactin also appears to promote tumor growth in the breast and prostate because these tissues have prolactin receptors, thereby setting up a feed-back loop that stimulates abnormal tissue growth.

Researchers at Ohio State have discovered how prolactin interacts with its receptor leading to a biological response. This knowledge has allowed them to develop variants of mammalian prolactin that interfere with an abnormal response to interaction between this hormone and its receptor in certain diseases. These prolactin antagonists work in humans as well as other mammals.

These agents will be useful for treatment of conditions where it is desirable to inhibit or decrease the action of prolactin especially but not restricted to:

  • Cancers that depend on prolactin for growth and survival such as some cancers of the breast, prostate and lymph system
  • Suppression of milk production in females after giving birth for women who do not plan to breast-feed
  • Suppression of prolactin secretion in patients that produce too much prolactin
  • Prevention of tumor formation in at-risk individuals
  • Prevention or reduction of cancer cell metastasis in the patient

An important feature of these compounds is that they can be administered in many different ways (oral, intravenous, intranasal or intratumor). With regard to treatment of cancer, the prolactin antagonists may be especially effective when used in combination with currently prescribed treatments for cancer.

Potential Applications:

Potential treatment for and/or prevention of breast and prostate cancers, as well as suppression of milk production in women after giving birth.

Advantages:

  • May be administered in a variety of manners including: oral, intravenous, intranasal or intratumor

Engineered Particulate Reinforcement of Polyimides

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Summary:

Researchers at the Ohio State University have discovered a new way to increase the toughness and the wear of materials by tuning particle characteristics. Plastics are often filled with inexpensive inorganic particles to improve the plastics’ wear and toughness. While it is well-known that these particles can provide significant benefits by simple property averaging, relatively little fine tuning of particle characteristics have taken place.

We have determined that these characteristics can have a dominant effect on the wear and toughness of a given polymer matrix, and this effect can be a more significant factor than the identity of the matrix itself. The results have borne this out: the toughness of a ""tuned"" commercial polyimide, Superimide 800, increased by a factor of ten over the unadulterated material. The large improvement that can be made to existing and new materials by simply fine tuning the characteristics of inorganic particles will have a significant impact on commericial airline, automotive, and other transportation industries that either use or will use polyimides as high temperature lightweight plastics.

Potential Applications:

  • Dentistry
  • Aerospace
  • Biomedical
  • Electronics
  • Automotives

Differentially Expressed in Squamous Cell Carcinoma Gene 1

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Summary:

Researchers at The Ohio State University have provided a novel method for diagnosing and treating squamous cell carcinoma and prostate cancer. This invention is based upon the detection of a specific gene (serine protease gene) encoding a human protein called Differentially Expressed in Squamous Cell Carcinoma Gene-1 or “DESC1″. The invention also provides for DESC1 vectors, host cells, antibodies directed to DESC1 polypeptides, hybridization probes, and primers useful in the method of detecting DESC1 mRNA.

Squamous cell carcinoma is the second most common form of skin cancer. This condition is typically diagnosed by visual examination of the morphological characteristics (shape, form, arrangement, etc.) of tissue samples by a cytologist or pathologist. The potential for human error inherent in these methods has thus made it desirable to develop more reliable and efficient techniques. Investigation into the underlying genetics of the disease has led to the identification of several genes of interest. The DESC1 gene, for instance, is expressed in significant levels in epithelial tissues of the head, neck, oral mucosa, tonsils, prostate, testes, and skin in healthy individuals. However, the gene is repressed in squamous cell carcinoma of the head, neck, prostate, and testes, as compared to normal tissue specimens. It has also been determined that DESC1 is not expressed in colon carcinoma, lung carcinoma, melanoma, or HeLa cells. This gene may prove a useful marker for the detection and treatment of squamous cell carcinoma and other skin cancers.

Potential Applications:

  • Diagnosing squamous cell carcinoma, prostate cancer, and other epithelial cancers in a tissue sample.
  • Therapeutic gene to treat squamous cell carcinoma, prostate cancer, and other epithelial cancers.

Advantages:

  • Differential expression of DESC1 permits a novel and improved method for diagnosing squamous cell and prostate carcinoma without the need for visual examination.
  • Expression of DESC1 can be determined using conventional procedures.
  • Down regulation of DESC1 during the progression of squamous cell carcinoma may provide a basis for therapeutic targets.

Cytomegalovirus Disrupts Interferon-Gamma Signal Transduction

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Summary:

The present invention provides a method for reducing levels of JAK 1 and thereby blocking the signal transduction pathways that are employed by IFN? and other interferon molecules. In one embodiment, the method comprises the steps of: providing at least one cytomegalovirus (CMV) gene product selected from the group consisting of the CMV immediate early gene (IE) products, the CMV early gene (E) products, and combinations thereof; and introducing the CMV gene product or products into cells at levels sufficient to decrease the levels of JAK 1 in the cell. In another embodiment, the method comprises the steps of providing a DNA molecule that comprises at least one CMV IE gene, or at least one CMV E gene, a plurality of CMV IE genes, a plurality of CMV E genes, or combinations thereof; introducing the DNA molecule into the cell; and inducing the expression of CMV IE and E genes in the cell, wherein the expression of products encoded by the CMV IE and CMV E genes decreases the levels of JAK 1 in the cell.

Potential Applications:

For use in the knockout of IFN-g induced MHC class I and class II expression, antigen processing and antiviral effector molecules.

Advantages:

CMV gene product treatment is effective where there is no other possibility to eradicate certain viral infections like herpes.

Novel Compounds for the Prevention and Treatment of Cancer Metastasis

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Summary:

Prostate and breast cancers are the most common cancer in men and women respectively. Currently, the most common form of treatment is the use of cytotoxic agents, which usually have unwanted side effects.

OSU Researchers in collaboration with the University of Oklahoma have developed novel compounds and methods for the treatment and prevention of cancer metastatsis in subjects. The compounds described are keratinocyte growth factor receptor tyrosine kinase inhibitors. Keratinocyte Growth Factor (KGF) is a member of the fibroblast growth factor family (also designated FGF-7) that is produced in stromal tissue and stimulates DNA synthesis, proliferation and migration of epithelial cells in the breast and other tissue.

These compounds are useful in the treatment of cancers with over-expression of KGF receptors and can be used in combination treatments for cancers.

Potential Applications:

  • Potent KGFR inhibitors, which have the potential to treat both the prostate and breast cancers and other cancers over-express with KGFR.
  • The inhibitors can also serve as chemopreventive agents.

Advantages:

  • KGF enhances the motility and proliferation of cancer cells, and since KGF signaling appears to be an early event associated with the progression of many types of cancer, potent and selective KGFR inhibitors have the potential to be used in the treatment of as well as prevention of cancers.