Methods of Inhibiting Tumor Cell Aggressiveness Using The Microenvironment of Human Embryonic Stem Cells
First Claim
1. A composition comprising one or more isolated factors from a microenvironment of human embryonic stem cells.
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Abstract
The invention provides compositions comprising one or more isolated factors from a microenvironment of human embryonic stem cells (hESCs), including, but not limited to, Lefty and inhibitors of Nodal. The invention also provides methods of utilizing factors derived from human embryonic stem cells (hESC) and their microenvironment to treat and prevent tumor formation and progression and to inhibit tumor cell aggressiveness. The invention further provides methods of inhibiting tumor cell growth and/or treating aggressive tumors in a mammal comprising administering to the mammal, having at least one tumor cell present in its body, an effective amount of an inhibitor of Nodal activity.
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Citations
44 Claims
- 1. A composition comprising one or more isolated factors from a microenvironment of human embryonic stem cells.
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4. An isolated Lefty protein produced by conditioning a matrix with human embryonic stem cells.
- 5. A protein comprising glycosylated Lefty or a fragment or derivative thereof.
- 10. A method of using one or more factors from a microenvironment of human embryonic stem cells to inhibit tumor cell aggressiveness.
- 15. A method of inhibiting tumor cell growth and/or treating aggressive tumors in a mammal comprising administering to the mammal, having at least one tumor cell present in its body, an effective amount of an inhibitor of Nodal activity.
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35. A method of inhibiting tumor cell growth in a mammal comprising administering to the mammal, having at least one tumor cell present in its body, an effective amount of a preconditioned microenvironment, which has been in contact with human embryonic stem cells.
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36. A method of detecting aggressive tumor cells comprising the steps of:
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a. obtaining a sample from a patient;
b. assaying the sample for the presence of Nodal and Lefty; and
c. detecting aggressive tumor cells if Nodal is present and Lefty is absent in the sample. - View Dependent Claims (37, 38)
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39. A method of identifying a compound for treating aggressive tumors, comprising:
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a. providing a plurality of cells that express Nodal;
b. assaying the cells for Nodal activity in the presence and absence of a candidate compound; and
c. identifying the compound as a compound for treating aggressive tumors if the Nodal activity is less in the presence of the candidate compound than in the absence of the candidate compound.
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40. A method for monitoring the effectiveness of a pharmaceutical composition as an agent for treating aggressive tumors in a patient comprising the steps of:
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a. obtaining a sample from a patient;
b. assaying the sample for the presence of Nodal;
c. administering an amount a pharmaceutical composition to the patient;
d. repeating steps (b) and (c) on subsequently-collected samples from the patient; and
e. comparing the amount of Nodal detected in the sample from step (a) with the amount of Nodal detected in the samples from step (d), wherein the effectiveness of the pharmaceutical composition is monitored by detecting changes in the amount of Nodal in the subsequently-collected samples compared with the sample taken in step (a).
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41. A method for detecting the presence of aggressive tumor cells comprising the steps of:
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a. obtaining a sample of tumor cells from a patient;
b. conducting a sequence based methylation analysis of the Nodal CpG island in the tumor cells;
c. comparing the degree of methylation in the CpG island of Nodal in the tumor cells to that of non-aggressive or non-tumor cells;
d. correlating hypermethylation of Nodal with the presence of aggressive tumor cells.
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42. A method for detecting the presence cells having a dedifferentiated, multipotent plastic phenotype in a mammal comprising the steps of:
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a. obtaining a sample from a mammal;
b. assaying the sample for the presence of Nodal;
c. correlating the presence of Nodal with the presence cells having a dedifferentiated, multipotent plastic phenotype. - View Dependent Claims (43, 44)
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Specification