Oncofetal fibronectin as a marker for health and disease
Methods and products for the detection of oncofetal fibronectin indicating molecules in samples are provided. Methods for imaging of oncofetal fibronectin are provided. In some methods provided herein, the sample is treated with a reagent and/or contacted with a non-specific binder. Provided are methods for testing subjects to ascertain health and disease status and to assess the risk of developing a disease or condition. Methods for detecting the presence of oncofetal fibronectin indicating molecules by a variety of methods such as immunoassays and mass spectrometry also are provided. Methods and products for detection of oncofetal fibronection for selection of concepti are provided.
1 . A method of detecting the presence of cancerous or pre-cancerous cervical cells in a subject, comprising:
testing for an oncofetal fibronectin indicating molecule in a sample from a subject, wherein:
the sample is selected from among urine, cervical interstitial fluid, blood, plasma and serum; and
an oncofetal fibronectin positive sample indicates the presence of cancerous or pre-cancerous cervical cells in the subject.
2 . The method of claim 1 , wherein the sample is collected with a swab selected from among a polyester swab, a cotton swab and a rayon swab.
3 . The method of claim 1 , wherein an amount of oncofetal fibronectin indicating molecule in the sample at or above a threshold identifies the sample as oncofetal fibronectin positive.
4 . The method of claim 1 , wherein an amount of oncofetal fibronectin indicating molecule in the sample below a threshold identifies the sample as oncofetal fibronectin negative.
5 . The method of claim 1 , wherein testing further comprises:
contacting the sample with a first fibronectin or oncofetal fibronectin binding partner; and
detecting complexes of the binding partner and oncofetal fibronectin indicating molecule.
6 . The method of claim 5 , wherein:
testing further comprises contacting the sample with a second fibronectin or oncofetal fibronectin binding partner, wherein: the second fibronectin or oncofetal fibronectin binding partner is conjugated to a detectable or bindable moiety, or the second fibronectin or oncofetal fibronectin binding partner is immobilized to a solid support; and
detecting complexes of the first binding partner, the second binding partner, and the oncofetal fibronectin indicating molecule.
7 . The method of claim 5 , further comprising:
contacting the sample with a non-specific binding compound prior to detecting complexes.
8 . The method of claim 5 , wherein:
the first binding partner is conjugated to a detectable moiety.
9 . The method of claim 5 , further comprising:
contacting the sample with a detectable compound that specifically binds the first binder after contacting the first binding partner and sample.
10 . The method of claim 9 , wherein the detectable compound is an antibody conjugate or a nucleic acid conjugate.
11 . The method of claim 6 , wherein the first binding partner is an anti-fibronectin antibody, or a fragment thereof.
12 . The method of claim 6 , wherein the second binding partner is an anti-fibronectin antibody, or a fragment thereof.
13 . The method of claim 1 , wherein the sample is contacted with a non-specific binding compound.
14 . The method of claim 1 , wherein:
the amount of oncofetal fibronectin indicating molecule detected is compared to two or more thresholds; and
the sample is classified according to the highest threshold that is less than or equal to the detected amount of oncofetal fibronectin indicating molecule, whereby classification of oncofetal fibronectin indicating molecule in the sample according to the highest threshold identifies an indication selected from among a risk of the subject developing cancerous cells, a likelihood of a subject developing cancerous cells and aggressiveness of cancerous cells.
15 . The method of claim 5 , wherein:
the complex is detected by measuring the oncofetal fibronectin indicating molecule that is bound to the fibronectin or oncofetal fibronectin binding partner, or a fragment of the oncofetal fibronectin indicating molecule that binds to the fibronectin or oncofetal fibronectin binding partner.
16 . The method of claim 15 , wherein the oncofetal fibronectin indicating molecule is detected by mass spectrometry or gel electrophoresis.
17 . The method of claim 5 , wherein:
the complex is detected by detecting the molecular weight of compounds bound to the fibronectin or oncofetal fibronectin binding partner; wherein a molecular weight that corresponds to an oncofetal fibronectin indicating molecule indicates the presence of the oncofetal fibronectin indicating molecule in the sample.
18 . The method of claim 17 , wherein the oncofetal fibronectin indicating molecule or fragment thereof is detected by mass spectrometry or gel electrophoresis.
19 . The method of claim 5 , wherein the complex is detected by detecting the fibronectin or oncofetal fibronectin binding partner bound to the oncofetal fibronectin indicating molecule.
20 . The method of claim 6 , wherein:
the fibronectin or oncofetal fibronectin binding partner is detected by detecting the moiety.
21 . The method of claim 6 , wherein at least one fibronectin or oncofetal fibronectin binding partner is immobilized to a test strip.
22 . The method of claim 1 , wherein the cells are hyperplastic, neoplastic or malignant.
23 . A method of detecting an oncofetal fibronectin indicating molecule in tissue or cells of a subject, comprising:
administering to a subject a fibronectin or oncofetal fibronectin binding partner conjugated to an imaging moiety, whereby the conjugate localizes to tissue or cells in the subject containing an oncofetal fibronectin indicating molecule; and
detecting the localization of the conjugate within the subject,
thereby detecting the oncofetal fibronectin indicating molecule in tissue or cells of the subject, wherein detection is indicative of cancer or a disease state characterized by the presence of oncofetal fibronectin.
24 . The method of claim 23 , wherein the tissues or cells are cervical tissues or cells.
25 . A method of treating tumorous tissue in a subject, comprising topically administering to a subject a fibronectin or oncofetal fibronectin binding partner, whereby the binding partner localizes to surfaces on the subject containing an oncofetal fibronectin indicating molecule, whereby the localized binding partner causes cell death or inhibits cell growth, whereby the cell death or cell growth inhibition caused by the binding partner inhibits tumor proliferation in the subject.
26 . A method for inhibiting the recurrence of neoplastic disease in a subject, comprising:
treating a subject for neoplastic disease; and
administering to the treated subject a fibronectin or oncofetal fibronectin binding partner, whereby recurrence of neoplastic disease is inhibited.
27 . The method claim 26 , wherein the neoplastic, malignant or metastatic cells are cells selected from among lung, breast, ovary, stomach, pancreas, larynx, esophagus, testes, liver, parotid, biliary tract, colon, rectum, cervix, uterus, endometrium, kidney, bladder, prostate, thyroid, pituitary, eye, brain, oral, skin, head and neck cancer, lymphoma, leukemia, squamous cell carcinoma, adenocarcinoma, small cell carcinoma, melanoma, glioma, sarcoma and neuroblastoma.
28 . A method of determining the overall health state of a subject, comprising testing for the presence of an oncofetal fibronectin indicating molecule in a sample from a subject, wherein:
the presence of oncofetal fibronectin indicating molecule in the sample indicates that the subject has a disease characterized by the presence of oncofetal fibronectin; and
the absence of oncofetal fibronectin indicating molecule indicates that the subject is free of a disease characterized by oncofetal fibronectin.
29 . The method of claim 28 , wherein the presence and absence of oncofetal fibronectin are relative to a threshold level.
30 . The method of claim 29 , wherein the disease is selected from among neoplastic disease, arthritis, diabetic retinopathy and Dupuytren's contracture.
31 . The method of claim 28 , further comprising performing one or more additional tests to identify the disease.