Assay for detection of renal cell carcinoma
AssigneeMount Sinai Hospital
InventorsEleftherios Diamandis, Constantina Petraki
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Abstract
Methods for diagnosing and monitoring renal cell carcinoma in a subject comprising detecting kallikrein polypeptides, or polynucleotides encoding the polypeptides in a sample from the subject. The kallikrein polypeptides include kallikrein 5, kallirekin 6, kallikrein 10, and kallikrein 11.
Claims31
A method for detecting kallikrein polypeptides or polynucleotides encoding kallikrein polypeptides that are associated with renal cell carcinoma in a patient comprising:
- (a) taking a sample from a patient;
- (b) detecting or identifying in the sample one or more kallikrein polypeptides or polynucleotides encoding the kallikrein polypeptides wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (c) comparing the detected amount with an amount detected for a standard.
A method for detecting kallikrein polypeptides associated with renal cell carcinoma in a patient comprising:
- (a) obtaining a sample from a patient;
- (b) detecting in the sample one or more kallikrein polypeptides, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (c) comparing the detected amounts with amounts detected for a standard.
A method for diagnosing and monitoring renal cell carcinoma in a subject comprising detecting in a sample from the subject one or more kallikrein polypeptides, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein.
A method of detecting renal cell carcinoma in a patient, the method comprising comparing:
- (a) levels of kallikrein polypeptides in a sample from the patient, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (b) normal levels of expression of the kallikrein polypeptides in a control sample, wherein a significant difference in levels of kallikrein polypeptides, relative to the corresponding normal levels, is indicative of renal cell carcinoma.
A method for monitoring the progression of renal cell carcinoma in a patient, the method comprising:
- (a) detecting in a sample from the patient at a first time point, kallikrein polypeptides, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- (b) repeating step (a) at a subsequent point in time;
- and (c) comparing levels detected in steps (a) and (b), and thereby monitoring the progression of renal cell carcinoma.
A method for determining in a patient whether renal cell carcinoma has metastasized or is likely to metastasize in the future, the method comprising comparing (a) levels of kallikrein polypeptides, in a patient sample, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (b) normal levels or non-metastatic levels of the kallikrein polypeptides, in a control sample wherein a significant difference between the levels of expression in the patient sample and the normal levels or non-metastatic levels is an indication that the renal cell carcinoma has metastasized.
A method for assessing the aggressiveness or indolence of renal cell carcinoma comprising comparing:
- (a) levels of expression of kallikrein polypeptides, in a patient sample, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (b) normal levels of expression of the kallikrein polypeptides, in a control sample, wherein a significant difference between the levels in the patient sample and normal levels is an indication that the cancer is aggressive or indolent.
A method for diagnosing and monitoring renal cell carcinoma in a sample from a subject comprising isolating polynucleotides from the sample, and detecting in the sample polynucleotides encoding kallikrein polypeptides, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein.
A method for determining the presence or absence of renal cell carcinoma in a subject comprising:
- (a) contacting a sample obtained from the subject with oligonucleotides that hybridize to polynucleotides encoding kallikrein polypeptides, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (b) detecting in the sample levels of nucleic acids that hybridize to the polynucleotides encoding kallikrein polypeptides relative to a predetermined cut-off value, and therefrom determining the presence or absence of renal cell carcinoma in the subject.
A method for assessing the potential efficacy of a test agent for inhibiting renal cell carcinoma in a patient, the method comprising comparing:
- (a) levels of kallikrein polypeptides, and/or polynucleotides encoding same in a first sample obtained from a patient and exposed to the test agent, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11, and (b) levels of the kallikrein polypeptides and/or polynucleotides encoding same in a second sample obtained from the patient, wherein the sample is not exposed to the test agent, wherein a significant difference in the levels of expression of the kallikrein polypeptides and/or polynucleotides encoding same in the first sample, relative to the second sample, is an indication that the test agent is potentially efficacious for inhibiting renal cell carcinoma in the patient.
A method of assessing the efficacy of a therapy for inhibiting renal cell carcinoma in a patient, the method comprising comparing:
- (a) levels of kallikrein polypeptides and/or polynucleotides encoding same in a first sample obtained from the patient, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11, and (b) levels of the kallikrein polypeptides and/or polynucleotides encoding same in a second sample obtained from the patient following therapy, wherein a significant difference in the levels of expression of the kallikrein polypeptides and/or polynucleotides in the second sample, relative to the first sample, is an indication that the therapy is efficacious for inhibiting renal cell carcinoma in the patient.
A method of selecting an agent for inhibiting renal cell carcinoma in a patient the method comprising (a) obtaining a sample comprising cancer cells from the patient;
- (b) separately exposing aliquots of the sample in the presence of a plurality of test agents;
- (c) comparing levels of kallikrein polypeptides and/or polynucleotides encoding same in each of the aliquots, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (d) selecting one of the test agents which alters the levels of kallikrein polypeptides and/or polynucleotides encoding same in the aliquot containing that test agent, relative to other test agents.
A method of inhibiting renal cell carcinoma in a patient, the method comprising (a) obtaining a sample comprising cancer cells from the patient;
- (b) separately maintaining aliquots of the sample in the presence of a plurality of test agents;
- (c) comparing levels of kallikrein polypeptides and/or polynucleotides encoding same in each of the aliquots, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- and (d) administering to the patient at least one of the test agents which alters the levels of kallikrein polypeptides and/or polynucleotides encoding same in the aliquot containing that test agent, relative to other test agents.
A method of assessing the renal cell carcinoma cell carcinogenic potential of a test compound, the method comprising:
- (a) maintaining separate aliquots of renal cell carcinoma cells in the presence and absence of the test compound;
- and (b) comparing expression of kallikrein polypeptides and/or polynucleotides encoding same, in each of the aliquots, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11, and wherein a significant difference in levels of kallikrein polypeptides and/or polynucleotides encoding same in the aliquot maintained in the presence of the test compound, relative to the aliquot maintained in the absence of the test compound, is an indication that the test compound possesses renal cell carcinoma cell carcinogenic potential.
An in vivo method for imaging renal cell carcinoma comprising:
- (a) injecting a patient with agents that bind to kallikrein polypeptides, the agents carrying labels for imaging the renal cell carcinoma, and wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11;
- (b) allowing the agents to incubate in vivo and bind to the kallikrein polypeptides;
- and (c) detecting the presence of the labels localized to the renal cell carcinoma.
A method of inhibiting renal cell carcinoma in a patient at risk for developing renal cell carcinoma, the method comprising inhibiting expression of genes encoding kallikrein polypeptides, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10 and kallikrein 11.
A kit for assessing whether a patient is afflicted with renal cell carcinoma, the kit comprising reagents that specifically bind with kallikrein polypeptides, wherein the kallilcrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11.
A kit for assessing the suitability of each of a plurality of agents for inhibiting renal cell carcinoma in a patient, the kit comprising:
- (a) the plurality of agents;
- and (b) reagents for detecting kallikrein polypeptides, wherein the kallikrein polypeptides comprise or are selected from the group consisting of kallikrein 5, kallikrein 6, kallikrein 10, and kallikrein 11.
Dependencies are inferred from the claim text.