Treatment of DNA damage related disorders

a dna damage and disorder technology, applied in the field of dna damage related disorders, can solve the problems of cancer risk, cancer risk, and subject's caner risk, and achieve the effects of inhibiting cancer invasion, shrinking or eliminating tumors, and reducing or eliminating further growth of cancer

Inactive Publication Date: 2005-02-10
ST JUDE CHIILDRENS RES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0015] The invention further provides methods of therapeutically treating cancer comprising administering to a subject having a cancer an effective amount of a chloroquine compound whereby the cancer is therapeutically treated. Optionally, the cancer is other than a localized skin epithelialoma or carcinoma basal cell. Optionally, the cancer is other than skin cancer. Optionally, the treatment reduces or eliminates further growth of the cancer. Optionally, the treatment shrinks or eliminates the tumor. Optionally, the treatment inhibits invasion of the cancer into tissues of the subject and / or inhibits metastasis of the cancer.

Problems solved by technology

In some methods, the subject is at risk of cancer due to a genetic variation associated with increased risk of cancer.
In some methods, the subject is at risk of cancer due to viral infection.
In some methods, the subject is at risk of caner due to exposure to a carcinogen or irradiation.
In some methods, the subject is at risk of cancer due to exposure to X-rays.

Method used

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  • Treatment of DNA damage related disorders
  • Treatment of DNA damage related disorders
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Examples

Experimental program
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Effect test

example 1

Radioprotection Assay

[0122] HeLa cells were treated with 2 μg / ml of chloroquine for one hour, washed for one hour, and irradiated at 2 or 6 Gy. Subsequently, 1000 cells were plated and assessed for colony formation. Table 2 shows that exposure to chloroquine prior to irradiation increased cell survival by 30%.

TABLE 2TreatmentAverage Number of Colonies*Std. Dev.2 Gy44419.5Chloroquine + 2 Gy58021.26 Gy94.610.6Chloroquine + 6 Gy1298.6

*Averages were from five individual samples.

[0123] To test the possibility that chloroquine activation of ATM may cause radioprotection, C57 / BL6 mice were exposed to 8 Gy IR, a dose which kills approximately 80% of the mice at around two weeks. Death appears to result from hematopoietic toxicities. The day before total body irradiation (TBI), mice were either given an i.p. injection of chloroquine or chloroquine was added to the drinking water (5 mice—i.p. 1.75 mg / kg chloroquine; 5 mice—i.p. 3.5 mg / kg chloroquine; 5 mice—1.75 mg / kg chloroquine in drink...

example 2

Cancer Prevention

[0125] Transgenic mice expressing the c-myc oncogene under the control of the immunoglobulin enhancer (i.e., E1-myc mice) develop B-cell lymphomas and leukemias with relatively short latencies. Chloroquine was added to the drinking water of a cohort of Eμ-myc mice and the mice were observed for the development of B-cell malignancies. FIG. 4 demonstrates that 100% of the control transgenic mice developed malignancies within 100 days of birth while 0% of the transgenic mice on chloroquine developed tumors. After ˜120 days, half of the cohort of chloroquine-treated mice were taken off of chloroquine and the other half were switched to receiving a dose of chloroquine by i.p. injection once a week. Within ˜30 days, all of the transgenic mice taken off of the chloroquine had developed tumors while none of the mice receiving weekly i.p. injections developed cancer. At 10 months of age, these mice on weekly chloroquine remained cancer-free and appeared healthy and normal. ...

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Abstract

The present invention provides methods and compositions for prophylaxis and treatment of a variety of disorders including DNA damage related disorders, cancer, ischemia, oxidative stress, atherosclerosis, and stroke using a chloroquine compound.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS [0001] The present application is a continuation-in-part of attorney docket 29202-710.831 filed May 26th 2004, the US national phase of PCT US03 / 37838 filed Nov. 26, 2003, which is a continuation-in-part of 10 / 351,733 filed Jan. 24, 2003 and is also a continuation-in-part of U.S. Ser. No. 10 / 307,077, filed Nov. 27, 2002, all of which are incorporated herein by reference in their entirety for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] This invention was made in the course of research sponsored by the National Institutes of Health (NIH Grant Nos. CA71387). The U.S. government may have certain rights in this invention. BACKGROUND OF THE INVENTION [0003] Cancer is now the second leading cause of death in the United States. Over 1 million new cases of cancer are expected to be diagnosed in 2003 and over 500,000 people are expected to die of cancer. [0004] Cancer is typically trea...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4706A61K31/675C07K16/40C12N5/071C12Q1/48G01N33/68
CPCA61K31/4706A61K31/675C07K16/40C12N5/0602C12N2501/06G01N2800/52C12Q1/485G01N33/6812G01N33/6842G01N33/6893C12N2501/999Y02A50/30
Inventor KASTAN, MICHAELBAKKENIST, CHRISTOPHER
Owner ST JUDE CHIILDRENS RES HOSPITAL
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