Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Treatment of aml

A compound and leukemia technology, applied in the direction of medical preparations containing active ingredients, organic active ingredients, drug combinations, etc., can solve the problem of limited donors of compatriots

Inactive Publication Date: 2007-11-21
齐肯胡伊斯－格罗宁根学院(UMCG)
View PDF32 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, the availability of matched sibling donors is limited

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Treatment of aml
  • Treatment of aml
  • Treatment of aml

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Example 1: Effects of VEGF and VEGFR on the growth of leukemia cell lines HL-60 and TF-1 cells

[0086] Expression of VEGF, VEGFR-1 and VEGFR-2 was examined in TF-1, U937 and HL-60 cells by RT-PCR (Fig. 1) and by functional assay (Fig. 2). All three cell lines showed VEGF expression. HL-60 and U937 cells showed positive PCR bands in RT-PCR of VEGFR-1. None of the cell lines tested showed a PCR band for VEGFR-2.

[0087]To demonstrate functional VEGFR, recombinant (rec) VEGF was added to HL-60 and TF-1 cells in the absence of exogenous growth factors (serum-free state) 165 , and viable cells were counted by trypan blue stain exclusion after 24 hours of stimulation. with recVEGF 165 A dose-dependent enhancement of leukemia cell survival was found in TF-1 cells, up to 450% of control cells (100%). recVEGF in HL-60 cells 165 Induced increased cell viability up to 980% of control cells (Figure 2).

[0088] The importance of VEGF / VEGFR signaling can be highlighted by t...

Embodiment 2

[0091] Example 2: Effects of VEGF and PTK787 on the survival rate of leukemia cells in patients.

[0092] Analysis of VEGFR-1 and -2 and VEGF by RT-PCR in six primary AML samples 165 expression (Figure 1). In 5 of these 6 patients, mRNA could be isolated and RT-PCR performed. All 5 patients expressed various amounts of VEGF. A weak PCR band for VEGFR-1 was found in 4 of 5 patients. Patients 2, 3 and 6 expressed substantial amounts of VEGFR-2 transcripts, whereas patients 1 and 5 expressed no VEGFR-2 at all (Fig. 1).

[0093] Although VEGFR expression could not be assessed in all patient samples, determination of functional VEGFR was performed on all samples. Survival of leukemia cells under serum-free conditions showed a large variation in the absolute number of viable cells after 24 h in different patient samples (median: 23.5 × 10 3 Live cells; range: 6.6-78.1×10 3 Living cells).

[0094] With 5ng / ml recVEGF 165 , the survival rate of leukemia cells was increased by ...

Embodiment 3

[0095] Example 3: Effects of PTK787 and conventional AML drugs on the survival rate of leukemia cells in patients

[0096] Leukemic cells from patients were incubated with different doses of PTK787, and the drug resistance of leukemia cells was evaluated using a total cell killing assay. The in vitro resistance results for PTK787 are summarized in Table 1 and illustrated in FIG. 6 . Dose-response curves (Figure 6) and LC50 values ​​(Table 1) for individual patients are given.

[0097] Significant differences were found between individual patients. The expression of VEGFR-1 was weak in all patients, whereas the expression of VEGFR-2 varied from no expression to high expression levels. Patient samples with high VEGFR-2 expression and low VEGF expression (No.2 and 3) were sensitive to PTK787 inhibition, causing high leukemic cell cytotoxicity; while for patient 6 with high VEGFR-2 and VEGF expression, Addition of PTK787 to leukemia cell cultures showed intermediate results. T...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present Invention relates to a method of treating a warm-blooded animal having acute myeloid leukemia (AML) which is resistant to conventional chemotherapy, comprising administering to said animal a therapeutically effective amount of a compound of formula (I), wherein the radicals and symbols have the meanings as defined in the specification, together or in combination with a conventional compound or compound mixture useful in AML treatment, in particular a topoisomerase II inhibitor, an antimetabolite, or an antitumor antibiotic, for simultaneous, separate or sequential use; and to a pharmaceutical composition and a commercial package comprising said combination.

Description

technical field [0001] The present invention relates to a method for the treatment of warm-blooded animals, especially humans, suffering from leukemia, especially acute myeloid leukemia (AML), especially acute myeloid leukemia resistant to conventional chemotherapy, comprising Said animals are administered in combination or together with a therapeutically effective amount of a compound of formula (I) as defined herein, and conventional compounds or compound mixtures useful in AML therapy, in particular topoisomerase II inhibitors, antimetabolites or antitumor Antibiotics, and optionally at least one pharmaceutically acceptable carrier, for simultaneous, separate or sequential use; also relates to a pharmaceutical composition and commercial package comprising said combination. Brief description of the drawings: [0002] figure 1 [0003] RT-PCR (Reverse Transcription Polymerase Chain Reaction) results of Huvec, U937, TF-1 and HL-60 cell lines and patient leukemia cell sample...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/502A61K45/06
CPCA61K45/06A61K31/502A61P35/02A61K2300/00
Inventor E·S·J·M·德本特W·A·坎普斯
Owner 齐肯胡伊斯－格罗宁根学院(UMCG)
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com