Compositions and methods for treating and diagnosing cancer

A composition and biological technology, applied in the direction of biochemical equipment and methods, microbial measurement/testing, etc., can solve problems such as obstacles to reliable tumor measurement methods, and obstacles to the diagnosis and treatment of cancer patients

Inactive Publication Date: 2006-10-25
RGT UNIV OF MICHIGAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Although tremendous progress has been made in understanding the genetic changes that lead to cancer (e.g., breast cancer), the lack of reliable tumor assays for de novo human cancer cells has hampered the ability to understand the role of these mutations at the cellular level
Likewise, the lack of identified cancer markers for solid tumor stem cells hampers the development of diagnostic and therapeutic approaches for cancer patients, such as breast cancer patients

Method used

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  • Compositions and methods for treating and diagnosing cancer
  • Compositions and methods for treating and diagnosing cancer
  • Compositions and methods for treating and diagnosing cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1934] Establishment and analysis of solid tumor cell xenograft models

[1935] This example describes the generation of tumors in mice and the analysis of these tumors using human solid tumor cells from humans.

[1936] Materials and methods

[1937]Prepare mice. Eight week old female NOD-SCID mice were anesthetized by intraperitoneal injection of 0.2 ml ketamine / xylazine (300 mg ketamine and 20 mg xylazine in a volume of 4 ml. 0.02 ml of this solution was used per 20 g mouse). Dilute to 200 μl with HBSS. Mice were then treated with VP-16 (etoposide) by intraperitoneal injection (30 mg etoposide dose per 1 kg mouse, diluted to a final injection volume of 200 μl in serum-free HBSS). Simultaneously, place estrogen pellets subcutaneously on the nape of the mouse using a trocar. All tumor injections / implantations were performed 5 days after the procedure. In the following methods, mice were anesthetized as described above.

[1938] Transplantation of primary tumor...

Embodiment 2

[1976] Characterization of the Wnt / β-catenin pathway in human breast cancer tumors

[1977] This example describes how one characterized the Wnt / β-catenin pathway in human breast cancer using the xenograft model described above. The Wnt / β-catenin pathway plays a role in the proliferation and self-renewal of normal stem cells. Although a significant percentage of human breast cancers appear to have constitutive activity of this important pathway, unlike colon cancer, the pathway has not been clearly elucidated in humans. 84-89 role in the pathology of the disease. The xenograft model described above can be used to characterize the biological consequences of this pathway in human breast cancer tumors. These assays are performed using cancer cells and early passage xenograft tumors directly after removal from the patient.

[1978] Function of the Wnt / frizzled / β-catenin signaling pathway in multiple patient tumors. Rationale: Almost 90% of rectal cancers contain mutati...

Embodiment 3

[2015] Localization of β-catenin in tumorigenic cells

[2016] In normal hematopoietic cells, nuclear β-catenin is found only in the stem cell compartment. Reya et al. further demonstrated that β-catenin signaling is required for normal stem cell self-renewal. The recent complete subcellular localization analysis of β-catenin in tumorigenic and non-tumorigenic tumor 1 breast cancer cells further supports this concept. In general, the subcellular distribution of β-catenin in cancer cells is heterogeneous. In some cells, the protein is predominantly located in the outer membrane, while in others it is predominantly in the nucleus. The subcellular distribution of the protein is different in tumorigenic and non-tumorigenic cancer cells. β-catenin is mainly located in the cytoplasm of non-tumorigenic cancer cells, while it is mainly located in tumorigenic cells ( Figure 8 ) in the nucleus of the cell. When activated by Wnt signaling, β-catenin translocates from th...

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PUM

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Abstract

The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides gene expression profiles associated with solid tumor stem cells, as well as novel stem cell cancer markers useful for the diagnosis, characterization, and treatment of solid tumor stem cells.

Description

[0001] This application claims priority to US Provisional Application Serial No. 60 / 477,228, filed June 9, 2003, and US Provisional Application Serial No. 60 / 477,235, filed June 9, 2003. [0002] This invention was made with government support under Grant No. 5P01CA07513606 granted by the National Institutes of Health. The Government therefore has certain rights in this invention. field of invention [0003] The present invention relates to compositions and methods for the treatment, characterization and diagnosis of cancer. In particular, the present invention provides gene expression signatures associated with solid tumor stem cells and novel stem cell cancer markers for the diagnosis, characterization and treatment of solid tumor stem cells. Background of the invention [0004] Breast cancer is the most prevalent female malignancy in most industrialized countries, estimated to affect approximately 10% of the female populati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
Inventor M·F·克拉克刘睿
Owner RGT UNIV OF MICHIGAN
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