Anticancer Effect Enhancer

a technology of anticancer agent and enhancer, which is applied in the direction of biocide, heterocyclic compound active ingredients, drug compositions, etc., can solve the problems of inability to achieve effective anticancer agent, limitation of the therapeutic effect of anticancer agent on cancer, and inability to accelerate the death of cancer cells, etc., to achieve excellent therapeutic effect on cancer

Inactive Publication Date: 2008-02-14
NIPPON KAYAKU CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013] In accordance with the present invention, it is possible to provide an enhancing agent for effect of anticancer agent for achieving an excellent therapeutic effect on cancer.

Problems solved by technology

However, it has been also known that there is no anticancer agent which is effective on all types of cancer and there is a limitation for the therapeutic effect of anticancer agent on cancer.
Thus, according to those reports, even when anticancer agent is merely distributed in large quantities in cancer cells, death of cancer cells is not accelerated unless hypoxic condition in tumor tissues is improved.
However, in any of the reports, it is not proved that NO actually enhances the therapeutic effect of anticancer agent on cancer in human clinical medicine.
Thus, according to those reports, it is strongly suggested that, in establishing a therapy of cancer by anticancer agent in human clinical medicine, the use of NO has a possibility of causing adverse effects to patients such as increase or progress of cancer.
In view of such circumstances, in Non-Patent Document 1 for example, it is shown that resistance of cancer cell line to anticancer agent induced by hypoxic condition is improved by a NO donor in an experiment using cultured cells and, although such a finding will be surely valuable for showing one direction for future research, it is not possible to conclude from such a finding that a NO donor has an action of shrinking the cancer tissues or an action of enhancing the effect of anticancer agent.
However, issue of a jumped conclusion that a NO donor enhances the effect of anticancer agent only by appealing an increase in transition of an anticancer agent to tumor tissues by an increase in permeability through blood vessel without actual confirmation of enhancement of NO donor in the action of anticancer agent to cancer tissues even in animal experiment is not convincing at all under the present status where scientific evaluation for the action of NO to cancer is in chaos as mentioned above.
In fact, with regard to data showing that improvement in therapeutic effect for cancer was able to be achieved by that method, no data is available even for animal experiment in Patent Document 1.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

A Study of the Effect of Concomitant Use of NO Donors with Anticancer Agents on Response to Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer in a Prospective Randomised Controlled Trial

Characteristics of the Subjects

[0022] Sixty five patients with inoperable advanced non-small cell lung cancer (NSCLC) fit the following five criteria and were recruited in this study: (a) stage IIIB or stage IV; (b) no prior chemotherapy or radiotherapy; (c) good performance status: a performance status of 0-2 according to the Eastern Cooperative Oncology Group (ECOG) scale; (d) without brain metastasis; (e) adequate renal function, hepatic function, hematological function and cardiac function.

[0023] Of the 65 patients with advanced NSCLC, 31 patients had squamous cell carcinoma (19 patients in stage IIIB and 12 patients in stage IV), 29 patients had adenocarcinoma (9 patients in stage IIIB and 20 patients in stage IV), 5 patients had large cell carcinoma (4 patients in stage IIIB...

example 2

Concomitant Use of a NO Donor, Nitroglycerin, Improves Chemosensitivity in Murine Lung Cancer Model

Methods

[0033] Murine Lewis lung carcinoma (LLC) cells, lung adenocarcinoma cells, were obtained from the Tohoku University Cell Resource Center for Biomedical Research and were incubated with DMEM plus 10% fetal bovine serum until cell proliferation was sufficient to perform the experiments. The LLC cells were adjusted to concentrations of 2×105 cells / 100 μl with phosphate buffer saline (PBS), and were inoculated Six-week-old male C57BL6 mice purchased from Charles River Japan, Inc. (Tokyo, Japan) and Clea Japan, Inc. (Tokyo, Japan) subcutanously (2×105 cells / 100 μl / mouse) at the right hypochondrium. Mice were maintained under specific-pathogen-free conditions, and provided with sterile food and water. When transplanted tumors grew to approximately 100 mm3 in tumor volume, animals were equally divided into four groups (Control group, n=6; C, NO donor group, n=6; N, Chemotherapy grou...

example 3

Concomitant Use of a NO Donor, Nitroglycerin, Improves Chemosensitivity in Murine Colon Cancer Model

Methods

[0036] Colon 26 cells, murine colon cancer cells, were obtained from the Tohoku University Cell Resource Center for Biomedical Research and were incubated with RPMI 1640 plus 10% fetal bovine serum until cell proliferation was sufficient to perform the experiments. The colon 26 cells were adjusted to concentrations of 2×105 cells / 100 μl with phosphate buffer saline (PBS), and were inoculated Six-week-old female BALB / c mice purchased from Charles River Japan, Inc. (Tokyo, Japan) and Clea Japan, Inc. (Tokyo, Japan) subcutanously (2×105 cells / 100 μl / mouse) at the right hypochondrium. Mice were maintained under specific-pathogen-free conditions, and provided with sterile food and water. When transplanted tumors grew to approximately 100 mm3 in tumor volume, animals were equally divided into four groups (Control group, n=6; C, NO donor group, n=6; N, Chemotherapy group, n=6; CTX,...

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Abstract

An object of the present invention is to provide an enhancing agent for effect of anticancer agent for achieving an excellent therapeutic effect on cancer. The enhancing agent for effect of anticancer agent according to the present invention which is a solving means therefor is characterized in that a nitric oxide donor is an effective ingredient. In accordance with the present invention, an excellent therapeutic effect is able to be achieved on non-small cell lung cancer which is still in such a state that no effective therapeutic method has been established yet for a progressive cancer which is not operable and is one of cancers where chemotherapy is most difficult to apply.

Description

TECHNICAL FIELD [0001] The present invention relates to an enhancing agent for effect of anticancer agent for achieving an excellent therapeutic effect on cancer. BACKGROUND ART [0002] It has been well known that, as a result of vigorous research and development of anticancer agents for many years, various kinds of anticancer agents are now being used in chemotherapy to various types of cancer and therapeutic effect is achieved thereby. However, it has been also known that there is no anticancer agent which is effective on all types of cancer and there is a limitation for the therapeutic effect of anticancer agent on cancer. [0003] As one of the causes for the limitation in the therapeutic effect on cancer by anticancer agent, it has been reported that hypoxic condition inside the solid cancer participates in resistance to its therapy. For example, in Non-Patent Document 1 (Matthews N E, Adams M A, Maxwell L R, Gofton T E, Graham C H. Nitric oxide-mediated regulation of chemosensiti...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/34A61P35/00
CPCA61K31/34A61P13/08A61P13/10A61P35/00A61P35/02A61P35/04A61P43/00
Inventor YASUDA, HIROYASUYAMAYA, MUTSUONAKAYAMA, KATSUTOSHISASAKI, HIDETADA
Owner NIPPON KAYAKU CO LTD
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