University of Louisville Research Foundation, Inc

Advanced Cancer Therapeutics, LLC

Antisoma Research Limited

Donald Miller

John Olaf Trent

Paula J Bates

Xiaohua Xu

Mariusz Z Ratajczak

Magdalena Kucia

Janina Ratajczak

Shelia Diann Thomas

Kara Joyce Sedoris

Alexandra Sokolova

Francine Rezzoug

Methods for ex vivo expansion of very small embryonic like stem cells in the absence of feeder cells are provided. In some embodiments the methods include providing a plurality of VSELs; and growing the VSELs in a culture medium that includes a histone deacetylase inhibitor, luteinizing hormone, follicle-stimulating hormone, and optionally transforming growth factor beta in an amount that is sufficient to overcome quiescence of the VSELs. Also provided are feeder cell-free cell cultures, ex vivo expanded VSELs, pharmaceutical compositions that include the disclosed ex vivo expanded VSELs, methods for overcoming quiescence in VSELs, methods for re-establishing imprinting in VSELs, method for treating injuries to tissues in subjects, methods for repopulating cell types in subjects, methods for bone marrow transplantation, methods for treating radiation exposure in subjects, and methods that relate to regenerative medicine.

Methods and compositions for ex vivo expansion of very small embryonic-like stem cells (VSELs)

Quadruplex-forming guanine-rich nucleic acid sequences are useful in compositions and methods for inhibiting cellular growth and proliferation and inducing cell death. Compositions for treating a patient are provided, including (i) a safe and effective amount of a sequence having at least 80% nucleic acid identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and combinations thereof, and (ii) a carrier, wherein the isolated oligonucleotide forms at least one quadruplex.

Compositions and methods for treating cancer, inhibiting cell proliferation, and inducing cell death

The present invention provides a method for inhibiting the proliferation of malignant and/or hyperplastic cells in a subject by administering to the subject a therapeutically effective amount of a guanosine rich oligonucleotide. The present invention also provides oligonucleotides which are capable of being specifically bound to a specific cellular protein which is nucleolin and/or nucleolin in nature, which is implicated in the proliferation of cells, specifically malignant and/or hyperplastic cells, and a method for their selection.

Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin

Methods for the treatment of tumors and cancer by exploiting the surface expression of the usually nuclear-localized protein, nucleolin.

Method for the diagnosis and prognosis of malignant diseases

Quadruplex-forming guanine-rich nucleic acid sequences are useful in compositions and methods for inhibiting cellular growth and proliferation and inducing cell death. Compositions for treating a patient are provided, including (i) a safe and effective amount of a sequence having at least 80% nucleic acid identity with a guanine-rich promoter gene oligonucleotide (GPGO), and (ii) a carrier, wherein the oligonucleotide forms at least one quadruplex.

Compositions and methods for treating cancer, inhibiting proliferation, and inducing cell death

Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and/or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

Methods for the diagnosis of cancer by determining the neoplastic status of a cell by probing the cell plasma membrane for the presence of nucleolin are provided, as are kits to carry out such tests.

The present invention provides a method for inhibiting the proliferation of malignant and/or hyperplastic cells in a subject by administering to the subject a therapeutically effective amount of a guanosine rich oligonucleotide. The present invention also provides oligonucleotides which are capable of being specifically bound to a specific cellular protein which is nucleolin and/or nucleolin-like in nature, which is implicated in the proliferation of cells, specifically malignant and/or hyperplastic cells, and a method for their selection.

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Louisville, KY, United States of America

Donald Miller