Combination methods of treating cancer

A cancer, subject technology, used in drug combinations, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve problems such as opportunistic infections

Inactive Publication Date: 2009-08-19
RAMOT AT TEL AVIV UNIV LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Purine analogues induce significant clinical improvement but are inevitably accompanied by immunosuppression, leading to opportunistic infections (19)

Method used

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  • Combination methods of treating cancer
  • Combination methods of treating cancer
  • Combination methods of treating cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0246] Example 1 - Materials and methods

[0247] Chemicals:

[0248]Methyl jasmonate [methyl 3-oxo-2-(2-pentenyl)cyclopentaneacetic acid], 2-deoxy-D-glucose (2DG) were purchased from Sigma-Aldrich Chemie GmbH (Steinheim, Germany) , 1,3-bis{2-chloroethyl}-1-nitrosourea (BCNU) and cisplatinum(II) dichloride (cisplatin). Doxorubicin was purchased from Pharmacia Italia S.p.A and paclitaxel was purchased from MeadJohnson (USA). Methyl jasmonate was dissolved in absolute ethanol to obtain a 500 mM stock solution. Further dilute MJ and cytotoxic drugs in culture medium. The final concentration of ethanol in the culture did not exceed 0.6%. For in vivo experiments, doxorubicin was dissolved in phosphate buffered saline.

[0249] Tumor cell lines:

[0250] CT26 is a murine colon carcinoma. DA-3 is a murine mammary adenocarcinoma. TRAMP C1 is a murine prostate carcinoma. MCF7 is human breast cancer. MIAPaCa-2 is a human pancreatic carcinoma. D122 is murine lung cancer. ...

Embodiment 2

[0264] Example 2: Cytotoxic effect of MJ on tumor cell lines in vitro

[0265] The cytotoxic activity of MJ against 6 adherent cell lines and 1 ex vivo mouse cell line was tested in vitro. Each cell line was exposed for 24 hours with MJ at concentrations ranging from 0.1 mM to 2 mM, and cytotoxicity was determined as described in Methods. Table 1 summarizes the IC50 values. As shown in Figure 1, MJ at a concentration of 0.25 mM or higher exerted cytotoxic effects. All cell lines responded to MJ in a dose-dependent manner.

[0266] Table 1: IC50 of MJ in different cell lines

[0267] IC50 value MJ(mM) D122

Embodiment 3

[0268] Example 3: Cytotoxic effect of combination therapy of MJ and chemotherapeutic drugs on cancer cell lines in vitro

[0269] The synergistic effect of MJ and traditional chemotherapeutic drugs was examined. Anticancer agents are rarely used as monotherapy. Effective chemotherapy often relies on the appropriate and effective combination of two or more agents. Four drugs with different modes of action are selected. The synergy of the combination of BCNU, cisplatin, paclitaxel and doxorubicin with a fixed concentration of MJ was evaluated in 7 cell lines. Based on dose response data (Figure 1) the concentration of MJ was chosen such that the cytotoxicity of MJ did not exceed 40%. An interaction of MJ with another agent is considered to be positive when the difference between the cytotoxicity of the two drugs when they are present and the sum of the cytotoxicities produced by each drug administered alone (the expected additivity in the figure) is pV<0.05 Cooperative (supe...

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PUM

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Abstract

The present invention relates to compositions and methods for treating cancer, by administering a combination comprising a jasmonate derivative (e.g., methyl jasmonate or a compound of any of formulae I through VII or any of the jasmonate derivatives exemplified by such formulae) and at least one other agent selected from a chemotherapeutic agent (e.g., a nitroso-urea, a platinum compound, a taxane derivative, an antitumor antibiotic) and an inhibitor of glycolysis (e.g., 2-deoxy-D-glucose). The jasmonate derivative and the at least one other agent together provide a therapeutic effect, which is preferably synergistic (cooperative).

Description

technical field [0001] The present invention relates to the treatment of cancer using a combination therapy comprising a jasmonate derivative in combination with a chemotherapeutic agent and / or an inhibitor of glycolysis. Background of the invention [0002] Jasmonates are a family of plant stress hormones obtained from linolenic acid via the octadecanoid pathway, which are present in small amounts in many edible plants. Stress hormones, such as the jasmonate family, are already formed in plants and are released at moments of stress such as severe UV radiation, osmotic shock, heat shock, and pathogen attack to initiate multiple cascades that culminate in an appropriate response . Examples of members of the jasmonate family are jasmonate (which is important for intracellular signaling in response to injury) and methyljasmonate (MJ) (which causes the induction of protease inhibitors), which respond to injury or pathogens Attacks accumulate at low concentrations. US Patent N...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/122A61K31/17A61K31/337A61K31/7004A61K31/7036A61K33/24A61P35/00A61K33/243
CPCA61K31/7036A61K45/06A61K31/17A61K31/7004A61K31/337A61K33/24A61K31/122A61P35/00A61P35/02A61P35/04A61P43/00A61K33/243A61K2300/00
Inventor 以列色·弗莱舍爱丽娜·海菲茨马科斯·赫茨伯格
Owner RAMOT AT TEL AVIV UNIV LTD
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