TREATMENT OF TRIPLE NEGATIVE BREAST CANCER UTILIZING ANDROST-5-ENE-3b,17b-DIOL (b-AED), ANDROST-5-ENE-3b,7b,17b-TRIOL (b-AET) AND ESTRADIOL (E2)

a technology of androst-5-ene, androst-5-ene-3b,7b,17b-triol, which is applied in the field of animal models, can solve the problems of triple-negative breast cancer that does not respond to hormone therapy, and resistance to therapy and relapse of breast cancer

Inactive Publication Date: 2018-07-26
THE UNITED STATES OF AMERICA AS REPRESETNED BY THE SEC OF THE AIR FORCE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a hormone modulator for causing cellular apoptosis in triple-negative breast cancer cells. This hormone modulator includes at least one of Δ5-androsten-3β,7β,17β-triol and estradiol. The invention also provides a method of preparing this hormone modulator by combining two solutions containing specific components. The technical effect of this invention is to provide an effective treatment for triple-negative breast cancer by inducing cellular apoptosis in cancer cells.

Problems solved by technology

Therapy resistance and relapse of breast cancer are still major challenges for current medicine.
As a result, triple-negative breast cancers do not respond to hormone therapy (such as tamoxifen or aromatase inhibitors) or therapies that target HER2 receptors (trastuzumab).

Method used

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  • TREATMENT OF TRIPLE NEGATIVE BREAST CANCER UTILIZING ANDROST-5-ENE-3b,17b-DIOL (b-AED), ANDROST-5-ENE-3b,7b,17b-TRIOL (b-AET) AND ESTRADIOL (E2)
  • TREATMENT OF TRIPLE NEGATIVE BREAST CANCER UTILIZING ANDROST-5-ENE-3b,17b-DIOL (b-AED), ANDROST-5-ENE-3b,7b,17b-TRIOL (b-AET) AND ESTRADIOL (E2)
  • TREATMENT OF TRIPLE NEGATIVE BREAST CANCER UTILIZING ANDROST-5-ENE-3b,17b-DIOL (b-AED), ANDROST-5-ENE-3b,7b,17b-TRIOL (b-AET) AND ESTRADIOL (E2)

Examples

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Effect test

example 1

[0055]A non-toxic vehicle for administration of androstene hormones according to embodiments of the present invention was prepared from a first solution and a second solution. The first solution, comprising liposomal formulation, was placed in PEG 300 to a concentration of 5% and heated in a sonicating water bath to about 45° C. The second solution, comprising a selected hormone (one or more of 5Δ-androsten-3β, 17α-diol, 5Δ-androsten-3β, 17β-diol, or 5Δ-androsten-3β,7β,17β-triol), was placed in PEG 300 and heated in a sonicating water bath to about 45° C. The first and second solutions were then combine and stirred until dissolved.

[0056]Biological function was tested in 293T cells, which is a human embryonic cell line transformed with Large T antigen or SV40. This hypotriploid (polyploid) cell line is particularly useful in such transformation studies and has very distinct phenotypes when grown. All androstene hormone treatment applications were at concentrations of 25 μM.

[0057]FIG....

example 2

[0067]Hormone dependent, noninvasive, epithelial phenotype (ER / PR positive MCF-7 breast cancer cells) and hormone independent, invasive, mesenchymal phenotype (ER / PR negative MDA-MB-231 breast cancer cell) cell suspensions were acquired and prepared in complete medium (DMEM / F12, 10% FBS, 1% penicillin / streptomycin (Gibco)). Cellular concentration was adjusted to 2×105 cells / mL.

[0068]Androstene hormone solutions according to embodiments of the present invention were prepared from a first solution and a second solution. For the first solution, 3.0 mg of β-AED or β-AET was added to warm PEG 300 to prepare 50 mM stock. For the second solution, 10 μL of LIPOFECTAMINE (3:1 DOSPA:DOPE) was introduced to 100 μL of PEG 300, mixed, and incubated in a water bath at 42° C. for 30 min. The first and second solutions were then mixed in a sonicator water bath at 42° C. for 1 hr. The final concentration was 50 mM β-AED (or AET, as used).

[0069]A β-estradiol solution was also prepared by adding 2.7 m...

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Abstract

A hormone modulator for causing cellular apoptosis in triple-negative breast cancer cells. The hormone modulator includes at least one of Δ5-androsten-3β,17β-diol and Δ5-androsten-3β,7β,17β-triol and estradiol.

Description

[0001]Pursuant to 37 C.F.R. § 1.78(a)(4), this application claims the benefit of and priority to prior filed co-pending Provisional Application Ser. No. 62 / 449,205, filed Jan. 23, 2017, which is expressly incorporated herein by reference in its entirety.RIGHTS OF THE GOVERNMENT[0002]The invention described herein may be manufactured and used by or for the Government of the United States for all governmental purposes without the payment of any royalty.FIELD OF THE INVENTION[0003]The present invention relates generally to animal models and, more particularly, to animal models for educational and investigational uses.BACKGROUND OF THE INVENTION[0004]Breast cancer is the most commonly diagnosed type of cancer. Therapy resistance and relapse of breast cancer are still major challenges for current medicine. In fact, about one in eight (12%) women in the U.S. will develop invasive breast cancer during their lifetime.[0005]Triple-negative breast cancers comprise a very heterogeneous subset ...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K31/568A61K47/10A61K47/24A61P35/00A61K9/00
CPCA61K31/568A61K47/10A61K47/24A61K9/0019A61P35/00A61K2300/00A61K9/1271A61K31/573A61K31/565A61B10/02A61M1/90A61K39/39A61B17/32053A61B2017/00707G09B23/306G09B23/34
InventorSHAAK, THOMASWANG, SUIZHAO
OwnerTHE UNITED STATES OF AMERICA AS REPRESETNED BY THE SEC OF THE AIR FORCE