Methods, compositions and articles of manufacture for contributing to the treatment of cancers

a technology of compositions and articles, applied in the field of methods, compositions and articles of manufacture for contributing to the treatment of cancer, can solve the problems of reducing the effect of chemotherapy, reducing the effectiveness of chemotherapy, so as to achieve enhanced treatment and effective delivery of chemotherapeutic agents

Inactive Publication Date: 2007-02-08
THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009] The present invention is directed to the administration of endothelin agonists and a chemotherapeutic agent to contribute to the treatment of cancers including solid tumors. In particular, tumors have distinctive vasculature including an increased number of ETB receptors which, when bound, cause vasodilation. Because ETB receptors are vasodilators, an ETB receptor agonist, in combination with a chemotherapeutic agent, is useful in the treatment of a solid tumor, such as those found in breast cancers. The ETB receptor agonist can more effectively deliver chemotherapeutic agents to tumors resulting in enhanced treatment.

Problems solved by technology

One problem in the treatment of cancers is that an effective dose of a wide variety of potential chemotherapeutic agents is restricted by these agents' non-selective, highly toxic effect on normal tissues.
As a result, many patients suffer from the side effects of chemotherapy without reaping the benefits of the treatment.
The clinical utility of paclitaxel has been hampered, however, by its dose limiting toxicities including hypersensitivity, neutropenia and peripheral neuropathy.
Without constant nourishment from these developing blood vessels, the tumors become hypoxic and subsequently die.

Method used

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  • Methods, compositions and articles of manufacture for contributing to the treatment of cancers
  • Methods, compositions and articles of manufacture for contributing to the treatment of cancers
  • Methods, compositions and articles of manufacture for contributing to the treatment of cancers

Examples

Experimental program
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Effect test

example 1

Breast Tumor Model

Effect of IRL1620 and Paclitaxel on Breast Tumor Perfusion

[0045] The following studies were conducted to examine the systemic hemodynamics and regional circuitry effects of ET-1 in normal and breast tumor-bearing rats.

[0046] One extensively studied breast tumor model is the chemically induced rat mammary carcinogenesis model. van Zwieten, The rat as animal model in breast cancer research. Martinus Nijhoff Publishers, Boston, pg. 206 (1984); Dao et al., J Natl Cancer Inst, 71:201 (1983); Russo etal., J Natl Cancer Inst, 61:1439 (1978); Huggins et al., Science, 137 (1962); Huggins et al., Proc Natl Acad Sci USA, 45:1294 (1959). Chemically induced mammary tumorigenesis in rats is the model most closely resembling a human cancer. Russo et al., Lab Invest, 62:244 (1990). In terms of tissue architecture, the mammary gland of a rat is comparable to that of human women. It is formed by an epithelium that covers the ducts and alveoli and a stroma, the connective tissue ...

example 2

Effect of ET-1 Infusion on Systemic Hemodynamics and Blood Flow to the Mammary Tissue of Normal and Tumor-Bearing Rats.

[0059] MNU and saline treatments were performed as i.p. injections three months prior to the studies. Rats were palpated regularly starting four weeks after the treatments. Once tumors reached about 4-8 mm in diameter, experiments were initiated.

[0060] Rats were anesthetized with urethane (1.5 g / kg, i.p.) (Sigma Chemicals, St. Louis, Mo.). All surgical areas were shaved and cleaned with alcohol swabs. The left femoral vein was cannulated (PE 50 tubing, Clay Adams, Parsipanny, N.J.) for drug administration. The left femoral artery was cannulated (PE 50 tubing) and was used for withdrawal of reference blood sample in microsphere studies using a withdrawal pump (Model 22, Harvard Apparatus, South Natick, Mass.). The right femoral artery was cannulated (PE 50 tubing) and connected to a Gould P23 ID pressure transducer for recording the blood pressure on a Grass P7D p...

example 3

Effect of IRL1620 on Pharmacokinetics of Paclitaxel

[0079] Altering blood flow dynamics in the body can significantly affect the pharmacokinetics of a therapeutic moiety, and paclitaxel is known to have complex pharmacokinetic properties. See, for example, Sparreboom et al., Cancer Res 56:2112 (1996a); Gianni et al., J Natl Cancer Inst 87:1169 (1995b); Sonnichsen & Relling, Clin Pharmacokinet 27:256 (1994); Huizing et al., J Clin Oncol 11:2127 (1993); Brown et al., J Clin Oncol 9: 1261 (1991); Longnecker et al., Cancer Treat Rep 71:53 (1987); Wiemik et al., Cancer Res 47:2486 (1987b). It is therefore important to understand the impact of IRL1620 on the plasma pharmacokinetics of paclitaxel. The presently described study was therefore conducted to determine whether IRL1620, a selective ETB receptor agonist, alters the pharmacokinetics of paclitaxel in breast tumor bearing rats.

[0080] Virgin female Sprague Dawley rats (Harlan Co., Madison, Wis.), 48 days old (120-140g) were used for...

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Abstract

Methods, compositions and articles of manufacture for contributing to the treatment of cancers, including solid tumors, are disclosed. The methods, compositions and articles of manufacture can utilize an endothelin B agonist (ETB) to enhance the delivery and resulting efficacy of a chemotherapeutic agent.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. patent application Ser. No. 11 / 360,236 filed Jun. 28, 2006 (which claims the benefit of U.S. Provisional Patent Application Nos. 60 / 655,656; 60 / 655,654; and 60 / 655,643 all of which were filed on Feb. 22, 2005) which is a continuation-in-part of U.S. patent application Ser. No. 10 / 691,915 filed Oct. 23, 2003 which claims the benefit of U.S. provisional patent application No. 60 / 420,960, filed Oct. 24, 2002. The contents of all these applications are incorporated by reference herein in their entirety.FIELD OF THE INVENTION [0002] The present invention relates to methods, compositions and articles of manufacture for contributing to the treatment of cancers including solid tumors through administration of an endothelin agonist and a chemotherapeutic agent. BACKGROUND OF THE INVENTION [0003] Successful treatment of cancers, including solid tumors, remains an unfulfilled medical goal, despite...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/17A61K38/19A61K38/21A61K31/7072A61K31/704A61K31/519A61K31/4745A61K31/337A61K31/282
CPCA61K31/282A61K38/10A61K31/4745A61K31/513A61K31/519A61K31/704A61K31/7072A61K38/2013A61K38/21A61K38/2285A61K45/06A61K31/337A61K2300/00A61P13/08A61P35/00A61P43/00A61K38/16
Inventor GULATI, ANILREDDY, GURULENAZ, LUIGI
Owner THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
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