Multimeric Protein Toxins to Target Cells Having Multiple Identifying Characteristics

This technology relates to multimeric bacterial protein toxins which can be used to specifically target cells. Specifically, this is a modified recombinant anthrax toxin protective antigen (PrAg) that has been modified in several ways. First, the PrAg can be activated both by a metalloproteinase (MMP) and by urokinase plasminogen activator (uPA). Second, the native PrAg lethal factor (LF) binding site has been modified so that only a modified PrAg comprising two different monomers can bind anthrax LF.

Laminin A Peptides

This invention relates to peptides and derivatives thereof having laminin-like activity, as well as a pharmaceutical composition of the peptide. The peptides claimed include Serine-Isoleucine-Lysine-Valine-Alanine-Valine (SIKVAV). Methods for promoting increased adhesion and migration of epithelial cells is also disclosed. The peptides have wide usage in research, nerve regeneration and cancer treatment. For example, this invention may be useful as an adhesion and regeneration agent for nerve guides and as an adhesion agent for vascular prosthesis.

Activation of Recombinant Diphtheria Toxin Fusion Proteins by Specific Proteases Highly Expressed on the Surface of Tumor Cells

This invention relates to diphtheria toxin fusion proteins comprising a diphtheria toxin (DT) cell-killing component and a cell-binding component such as granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 2 (IL-2), or epidermal growth factor (EGF). Receptors for the latter three materials are present on many types of cancer cells; therefore, these fusion proteins bind preferentially to these cancer cells. A key feature is that these toxins are altered so as to require activation by a cell-surface protease that is overexpressed on many types of cancers.

Brother of the Regulator of Imprinted Sites (BORIS)

The subject application discloses an isolated or purified nucleic acid molecule consisting essentially of a nucleotide sequence encoding a human or a non-human BORIS, or a fragment of either of the foregoing; an isolated or purified nucleic acid molecule consisting essentially of a nucleotide sequence that is complementary to a nucleotide sequence encoding a human or a non-human BORIS, or a fragment of either of the following; a vector comprising such an isolated or purified polypeptide molecule consisting essentially of an amino acid sequence encoding a human or a non-human BORIS, or a fragme

Detection of Mutational Frequency in Human Bone Marrow

To date there have been no adequate methods to determine the frequency of mutations in humans. This invention discloses a method of measuring the mutational frequency of a mitochondrial DNA sequence by sequencing mitochondrial DNA from clonally expanded single cells such as CD34+ human stem cells. Sequencing for mitochondrial DNA polymorphisms and mutations may also be useful as a general method to detect minimal residual disease in leukemia. The mitochondrial genome is particularly susceptible to mutations and these may be used to measure genomic mutagenesis by virtue of comparison.

Compositions and Methods for Inhibiting Vascular Channels and Methods of Inhibiting Proliferation

Angiogenesis, the recruitment of new blood vessels, is recognized as an important factor in tumor proliferation in many types of cancer. It is generally accepted that therapeutic approaches that inhibit angiogenesis effectively limit, or even prevent, the formation of solid tumors. It has also been shown that anti-angiogenic therapeutics allow conventional radiation therapy and chemotherapy to be more effective.

This invention pertains to certain compounds that inhibit angiogenesis in a previously unrecognized way.

Methods of Screening for Risk of Cancer Using Human Lactoferrin DNA Probe or Primer

While normal breast ductal epithelium and neutrophilic granulocytes contain lactoferrin, their malignant counterparts frequently do not. The NIH announces primers or probes corresponding to the human lactoferrin gene, its promoter region, and its protein product, obtained from human breast tissue. The lactoferrin primer or probes can be used to screen for malignancy arising from tissues that normally secrete lactoferrin, or as a test to check the recovery of a patient from a malignancy.

Imaging of Extracellular Proteases in Cells Using Mutant Anthrax Toxin Protective Antigens

The claimed invention provides highly specific and sensitive methods for in vivo, in vitro, or ex vivo imaging of specific extracellular protease activity using an anthrax binary toxin system. The system targets cells that express extracellular proteases of interest. Such a system would be highly useful since various studies have demonstrated a positive correlation between the activity of extracellular proteases and various diseases and undesirable physiological conditions.

Vitamin D Receptor Antagonists for Treating Breast Cancer

Vitamin D receptor (VDR) is a nuclear receptor that is activated by calcitriol, the active form of vitamin D. It is best known for regulating dietary calcium uptake necessary for bone growth, but it also affects cell proliferation and differentiation. Therefore, it was thought that treatment with calcitriol or its derivatives could be useful to treat the uncontrolled proliferation typical of cancer cells. However, this approach has been unsuccessful to date because it leads to toxic levels of calcium in the blood.

Potent Nucleotide Inhibitors of Ecto-5'-Nucleotidase (CD73)

These small molecules are novel nucleotide derivatives, containing either a purine or pyrimidine nucleobase, that competitively block the enzyme CD73, also known as ecto-5'-nucleotidase. This enzyme converts extracellular AMP (not a potent activator of adenosine receptors) to adenosine (the native activator of 4 subtypes of adenosine receptors. CD73 inhibitors are being used, in clinical trials and preclinical research, in conjunction with cancer immunotherapy.