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Metabolomic profiling of prostate cancer

A technology of prostate cancer and metabolites, applied in the field of cancer markers, can solve the problems of elevated serum PSA levels and the inability to know the invasiveness of cancer

Inactive Publication Date: 2013-01-23
RGT UNIV OF MICHIGAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Elevated serum PSA levels are often detected in patients with non-malignant conditions such as benign prostatic hyperplasia (BPH) and prostatitis, and the aggressiveness of the cancer detected is unknown

Method used

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  • Metabolomic profiling of prostate cancer
  • Metabolomic profiling of prostate cancer
  • Metabolomic profiling of prostate cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0180] Biomarkers found in urine

[0181] general method

[0182] Identification of Metabolic Signatures in Prostate Cancer

[0183] Each sample was analyzed to determine the concentrations of several hundred metabolites. Analytical techniques such as GC-MS (Gas Chromatography-Mass Spectrometry) and UHPLC-MS (Ultra High Performance Liquid Chromatography-Mass Spectrometry) are used to analyze metabolites. Multiple aliquots were analyzed in parallel simultaneously and after appropriate quality control (QC), the information obtained from each analysis was recombined. Each sample is characterized according to thousands of properties that ultimately boil down to hundreds of chemical species. The technique used enables the identification of new chemically unnamed compounds.

[0184] Statistical Analysis

[0185] The data were analyzed using t-tests to identify molecules (known named metabolites or unnamed metabolites) that were present at different levels in definable populatio...

Embodiment 2

[0226] Validation of Multiple Metabolites in Prostate Cancer Tissues, Cell Lines, and Urinary Sediments

[0227] Materials and methods:

[0228] Amino acids were purchased from Sigma Corporation (St. Louis, MO, USA). Correspondingly labeled versions were purchased from Isotec Corporation (Miamisburg, OH, USA). Isobutanol, chloroform, methyl cyanide, dimethylformamide, ethyl acetate were purchased from Sigma. All other chemicals analyzed were reagent grade and purchased from Fluka and Sigma. n-methyl-N-(tert-butylmethylsilane trifluoroacetamide (MtBSTFA) + 1% tert-butyl-dimethylchlorosilane and heptafluorobutyrylic anhydride were purchased from Regis Technologies Inc, IL, USA.

[0229] clinical sample

[0230] Obtain benign prostate and localized prostate cancer tissue from radical prostatectomy series and metastatic prostate cancer biospecimens from expedited autopsy procedures at the University of Michigan Hospital, Michigan Specialized Program of Research Excellence in P...

Embodiment 3

[0260] Validation of metabolites in breast cancer tissues and cell lines

[0261] Validation of sarcosine in breast cancer tissue:

[0262] Sarcosine was identified as a differential metabolite at high levels in the progression of prostate cancer. GC-MS studies indicate a progression from benign to localized and then metastatic disease in the progression of cancer. Levels of many metabolites were elevated. Analysis using cell lines supports this observation. The same approach was applied to breast cancer samples. 19 tissue samples (10 benign, 8 localized and 1 metastatic breast cancer tissue) were analyzed. Breast cancer tissues showed higher sarcosine levels than corresponding benign tissues (Figure 31).

[0263] Creatine validation in invasive and non-invasive breast cancer cell lines:

[0264] Sarcosine validation was performed using a range of invasive (MDA-MB-231, BT-549, T578, SVM-245) and non-invasive (HME) breast cancer cell lines. The invasive cell lines showed...

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Abstract

The present invention relates to cancer markers. In particular, the present invention provides metabolites and panels of metabolites that are differentially present in cancer (e.g., prostate or breast cancer).

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Application No. 61 / 289,206, filed December 22, 2009. [0003] A note about federally funded investigations or research [0004] This invention was made with government support under Grant No. U01 CA111275 from the National Institutes of Health. The government has certain rights in this invention. technical field [0005] The present invention relates to cancer markers. In particular, the invention provides metabolites and groups of metabolites that are differentially present in cancer (eg, prostate cancer or breast cancer). Background technique [0006] Prostate cancer (PCA) has become the top killer of male cancer, second only to lung cancer, and the probability of men over 65 years old suffering from prostate cancer is as high as 1 / 9 (Abate-Shen and Shen, Genes Dev14: 2410 [2000]; Ruijter et al Endocr Rev, 20:22 [1999]). The American Cancer Society estimates that in 2001 ap...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68G01N33/574
CPCG01N33/493G01N33/57415G01N2800/60G01N33/57434
Inventor A.M.钱奈延T.拉詹迪兰
Owner RGT UNIV OF MICHIGAN
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