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Method of estimating antitumor effect of histone deacetylase inhibitor.

A technique for sirtuins and inhibitors, applied in the field of predicting the anti-tumor effect of histone sirtuin inhibitors

Inactive Publication Date: 2006-05-24
ASTELLAS PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still many unresolved issues: there are no reports of factors that can predict the antitumor effect of this compound, whether the results of in vitro tests can be directly applied in vivo, whether it shows useful effects in vivo for any tumor, etc.

Method used

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  • Method of estimating antitumor effect of histone deacetylase inhibitor.
  • Method of estimating antitumor effect of histone deacetylase inhibitor.
  • Method of estimating antitumor effect of histone deacetylase inhibitor.

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Evaluation of compound A sensitive tumors and compound A resistant tumors

[0075] (1) Reagent preparation

[0076]Weigh the necessary amount of FK228, add a solvent (10% HCO-60 / salt water), and perform ultrasonic dissolution. Before the start of the experiment, the positive control substance, paclitaxel, was dissolved in Cremophor EL / ethanol (1:1) solution and stored under refrigeration. When used, it was diluted by adding 9 times the amount of normal saline to make 2.4 mg / mL (solvent composition: 5% Cremophor EL-5% ethanol-90% saline).

[0077] (2) Experimental animals

[0078] In the anti-tumor test of the drug, BALB / cANnNCrJ-nu / nu mice (male, 6 weeks old) were purchased from Charles River of Japan and used for the test after being domesticated for one week or more. The mice are raised in an SPF environment and freely take in water and food.

[0079] (3) Experimental tumor

[0080] Divide 2~3×10 7 Human cultured kidney cancer cell line 1 (ACHN: obtained from ATCC) and hu...

Embodiment 2

[0091] Evaluation of compound A sensitive tumors and compound A resistant tumors

[0092]

[0093] (1) Experimental materials

[0094] Pharmaceutical Compound A (FK228)

[0095] Dosage: 3.2mg / kg

[0096] Dosing capacity: 10mL / kg

[0097] Solvent: 10% HCO-60 / saline solution

[0098] Dosage form: solution (when used)

[0099] Tumor cell human prostate cancer PC-3 (tumor section 3mm×3mm×3mm / mouse inoculation site s.c.)

[0100] Human gastric cancer SC-6; obtained by the Central Laboratory Animal Research Institute

[0101] (Tumor section 3mm×3mm×3mm / mouse inoculation site s.c.)

[0102] Human renal carcinoma ACHN (Tumor section 3mm×3mm×3mm / mouse transplantation site s.c.)

[0103] Human renal carcinoma A498; Obtained from ATCC (Tumor section 3mm×3mm×3mm / mouse inoculation site s.c.)

[0104] Subordinate animal male BALB c / nu / nu

[0105] (2) Sequence and result

[0106] According to the method shown in Example 1, a 3mm square tumor section (human prostate cancer PC-3, human gastric ca...

Embodiment 3

[0108] Analyze the gene expression patterns of compound A-sensitive tumors and compound A-resistant tumors by gene chip

[0109] In Example 2, gene expression patterns in tumors that can be confirmed as sensitive or resistant were studied.

[0110] (1) Experimental materials

[0111] Tumor cell human prostate cancer PC-3 (tumor section 3mm×3mm×3mm / mouse inoculation site s.c.)

[0112] Human gastric cancer SC-6; obtained from the Central Laboratory of Experimental Animals (Tumor Section 3mm×3mm×3mm / mouse inoculation site s.c.)

[0113] Human renal cancer ACHN (Tumor section 3mm×3mm×3mm / mouse inoculation site s.c.)

[0114] Human renal carcinoma A498; Obtained from ATCC (Tumor section 3mm×3mm×3mm / mouse inoculation site s.c.)

[0115] Subordinate animal male BALB c / nu / nu

[0116] RNA extraction Rneasy Mini Kit (50) (Qiagen)

[0117] RNase, DNase free water (Life Technologies)

[0118] DNA Synthesis Superscript Choice System (Life Technologies)

[0119] Etchachinmate(Nippon gene)

[0...

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Abstract

In order to provide genes that are effective in predicting the efficacy of histone deacetylase inhibitors on tumors that require treatment, especially for predicting anti-tumor effects, the present invention provides a drug that can be used as a histone deacetylase inhibitor. A method for genes that are indicators of effective prediction, the method at least includes the following steps: ① the step of classifying tumor cells into histone deacetylase inhibitor-sensitive tumor cells and resistant tumor cells; Tumor cells are individually studied for their gene expression patterns and genes are selected that are (i) highly expressed in competent tumor cells and low in resistant tumor cells, or (ii) low in competent tumor cells and low in resistant tumor cells Steps for genes with high expression in the middle.

Description

Technical field [0001] The present invention relates to a method for obtaining a gene that can be used to predict the efficacy of a histone deacetylase inhibitor, specifically, predicting the antitumor effect, and predicting the histone deacetylase including studying the expression of the gene Method of inhibitor's efficacy (anti-tumor effect). Background technique [0002] In recent years, “customized medical care” that takes into account individual differences of patients has gained attention, and it is necessary to seek for signs of cancer for which drugs are effective and ineffective. The content is to verify the effectiveness of the drug in advance, and then administer the drug to the patient, thereby improving the effectiveness of the drug, avoiding toxicity, inhibiting the use of meaningless drugs, and trying to improve the cost performance of the drug in the ethical and medical aspects . In addition, in cancer treatment, this can be used as an important means to fill the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/10C12Q1/68G01N33/50
CPCC12Q1/6886C12Q2600/106C12Q2600/112G01N33/5011G01N2333/916A61P35/00A61P43/00C12N15/10
Inventor 笹川由香直江吉则
Owner ASTELLAS PHARMA INC