Targeting pax2 for the treatment of breast cancer

A technology for breast cancer and breast diseases, applied in breast cancer vaccines, gene therapy, recombinant DNA technology, etc.

Inactive Publication Date: 2012-05-30
PHIGENIX INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

While most early-stage breast cancers are diagnosed based on finding abnormalities on breast imaging, a lump or change in the firmness of breast tissue can also be a warning sign of disease

Method used

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  • Targeting pax2 for the treatment of breast cancer
  • Targeting pax2 for the treatment of breast cancer
  • Targeting pax2 for the treatment of breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0200] Example 1: Human β-defensin-1 is cytotoxic to advanced prostate cancer and is at the forefront role in tumor immunity in adenocarcinoma

[0201] In this example, DEFB1 was cloned into an inducible expression system to test how it affects normal prostate epithelial cells as well as androgen receptor positive (AR+) and androgen receptor negative (AR-) prostate cancer cell lines. Induction of DEFB1 expression resulted in decreased cell growth of AR- cells DU145 and PC3, but had no effect on the growth of AR+ prostate cancer cells LNCaP. DEFB1 also causes rapid induction of caspase-mediated apoptosis. The data presented here provide the first evidence of a role for DEFB1 in innate tumor immunity and suggest that its impairment promotes tumor development in prostate cancer.

[0202] Materials and Methods

[0203] Cell lines: Cell line DU145 was grown in DMEM medium, PC3 in F12 medium, and LNCaP (Life Technologies, Inc., Grand Island, NY) in RPMI medium. Growth media f...

Embodiment 2

[0231] Example 2: SiRNA-mediated knockdown of PAX2 expression results independent of P53 status of prostate cancer cells die

[0232] In this example, the effect of inhibiting the expression of PAX2 was detected by RNA interference in prostate cancer cells with different p53 gene status. The results demonstrate that inhibition of PAX2 leads to cell death independent of p53 status, suggesting the presence of other tumor suppressor genes or cell death pathways that are inhibited by PAX2 in prostate cancer.

[0233] Materials and methods

[0234] siRNA Silencing of PAX2: To achieve efficient gene silencing, a pool of four complementary short interfering ribonucleotides (siRNAs) targeting human PAX2 mRNA (accession number NM_003989.1) was synthesized (Dharmacon Research, Lafayette, CO, USA). A second pool of four siRNAs was used as a loading control for testing PAX2 siRNA specificity. Two of the synthesized sequences targeted GL2 luciferase mRNA (accession number X65324), an...

Embodiment 3

[0270] Example 3: Inhibition of the PAX2 oncogene leads to DEFB1- mediated death

[0271]Identification of tumor-specific molecules as targets for the development of novel cancer drugs is considered a major goal of cancer research. Example 1 demonstrates that there is a high frequency of impaired DEFB1 expression in prostate cancer, and that induction of DEFB1 expression leads to rapid apoptosis in androgen receptor-negative prostate cancer. These data suggest a role for DEFB1 in prostate tumor suppression. Furthermore, given that it is a naturally occurring component of the immune system of normal prostate epithelial cells, DEFB1 is expected to be a viable therapeutic agent with few to no side effects. Example 2 demonstrates that inhibition of PAX2 expression leads to p53-independent prostate cancer cell death. These data suggest the presence of other pro-apoptotic factors or tumor suppressors that are inhibited by PAX2. Furthermore, data suggest that the oncogene fact...

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Abstract

The present application provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2. In the certain embodiments, the method of inhibiting expression of PAX2 is to administrate the subject a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 or by increasing expression of DEFB1 is also provided.

Description

[0001] This application claims priority to US Patent Application No. 12 / 708,294, filed February 18, 2010, and US Patent Application No. 12 / 546,292, filed August 24, 2009. Background of the invention [0002] Breast cancer is the most common cause of cancer in women and the second most common cause of cancer death in women in the United States. Although most early-stage breast cancers are diagnosed based on finding abnormalities on breast imaging, a lump or change in the firmness of breast tissue can also be a warning sign of disease. Increased awareness of breast cancer risk over the past few decades has led to an increase in the number of women undergoing mammographic screening, leading to earlier detection of cancer and thus improved survival rates. Still, breast cancer is the most common cause of death in women aged 45 to 55. [0003] Many types of cancer are known to be caused by genetic aberrations, or mutations. Accumulation of mutations and impairment of cellular cont...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K31/7105C12N15/113A61P35/00
CPCA61K31/7105A61K38/1729C12N2310/14C12N15/113A61P35/00A61K2039/812C07K16/18C07K16/3015A61K45/06
Inventor 卡尔顿·D·唐纳德
Owner PHIGENIX INC
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