Navigation Links
New mouse model for testing cancer drugs
Date:7/19/2011

FRANKFURT. Only one in twenty cancer drugs makes its way from the laboratory to become an approved pharmaceutical product. The majority of new agents are only shown to be unsuitable in the later phases of clinical development which would explain the exorbitantly high development costs of 500 to 600 million euros per new cancer drug. In order to recognize at an earlier stage which side effects are associated with the use of new cancer drugs, a research group under the guidance of the Goethe University has developed a new mouse model. In cooperation with the companies Bayer Schering Pharma AG and Taconic Artemis GmbH, the researchers were the first to simulate drug-induced inhi-bition what is currently one of the most attractive target genes for new cancer drugs. They were able to demonstrate that, as a result of this, the rapid division of cancer cells was prevented while healthy cells were hardly affected. This study has been published in the current issue of the prestigious journal, Nature Communications.

The cancer gene, polo-like kinase 1 (Plk1), which is currently the subject of intense investigation, plays a central role in cell division. However, up to now, it has not been possible with classical mouse model to investigate what would happen if this gene were to be silenced in adult animals since the latter is indispensable to embryonic de-velopment. The researchers working together with Prof. Klaus Strebhardt from the Centre for Gynecology and Obstetrics at Frankfurt's University Hospital thus devised a method of silencing the gene at any point during the lifetime of the new transgenic mouse. To this end, they expressed short RNAs with a length of 20 to 22 base pairs in the cells of the mice. These short RNAs prevent the information which is read by the cancer gene from being converted into proteins. This method known as RNA interfe-rence was further developed by the researchers into an inducible system: The design is such that the expression of Plk1-specific RNA and, in turn, the silencing of the gene is only induced by the antibiotic Doxycycline. The mice are therefore able to mature and the relevant gene is not knocked down using Doxycycline until the mice have reached adult age.

The working group supervised by Prof. Strebhardt in cooperation with Bayer Schering Pharma AG and Taconic Artemis GmbH developed the mouse model (Plk1 iKD animals). The mice were subsequently phenotypically characterized. This was done together with the Helmholtz Center in Munich, Munich's two universities as well as the universities of Gieen and Hamburg. "Surprisingly, despite the efficient knock-down of Plk1 in various tissues of the mouse following administration of Doxycycline over a six-week period, no major structural or functional anomalies were identified," reported Strebhardt. "This observation is diametrically opposed to the role of Plk1 in cancer cells of varying origins which, following the inhibition of Plk1, quickly cease dividing and go into apoptosis." In order to further verify the surprising findings in the Plk1 iKD animals, the researchers examined various primary cells in culture under controlled conditions. Just as previously in the animal experiment, Plk1 expression was inhibited through RNA interference and analyzed. In this system, too, the results of the animal experiments were confirmed: In contrast to tumor cells, healthy cells are only dependent on Plk1 expression to a minimal degree. As such, healthy cells are virtually undamaged if the Plk1 gene is silenced while the cancer cells are combated.

"Inducible RNAi-based mouse models represent an attractive way of reversibly con-trolling gene expression in order to study the targeted inactivation of genes. Our work is a feasibility study which considers whether inducible RNAi-based mouse models are suitable for predicting the toxicity of targeted cancer drugs," explained Klaus Strebhardt. "The similar results of the Plk1 knockdown in transgenic animals and cultivated primary cells have served to validate the preclinical relevance and the predictive value of the inducible iKD mouse model. This new animal model provides information on mechanism-based toxicities which could occur as a result of the pharmacological inhibition of Plk1. Our approach can be applied to many other can-cer-relevant target genes."


'/>"/>

Contact: Prof. Klaus Strebhardt
Strebhardt@em.uni-frankfurt.de
49-696-301-6894
Goethe University Frankfurt
Source:Eurekalert

Related medicine news :

1. Human Stem Cells Used to Fix Damaged Mouse Heart
2. Mouse Study Uncovers the Roots of Gray Hair
3. Mouse Study Reveals How Smoking Helps Keep People Thin
4. Apples Help Keep Muscles Strong, Mouse Study Finds
5. Scientists create humanized mouse model for hepatitis C
6. Pitt researchers build a better mouse model to study depression
7. Mouse study turns fat-loss/longevity link on its head
8. Fox Chase researchers report that naproxen reduces tumors in a mouse model of colon cancer
9. Sleeping through danger: the dormouse approach to survival
10. Mouse Sperm Successfully Grown in Lab, Researchers Say
11. Mouse cancer genome unveils genetic errors in human cancers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/26/2016)... ... , ... Development Team of Pixel Film Studios Announced The Release of TranSweep, ... transition tool will keep a consistent flow to your project while adding interesting visuals ... TranSweep is an all new layered style transition tool for Final Cut Pro ...
(Date:5/26/2016)... , ... May 26, 2016 , ... In Madeira Beach ... mainland by a single drawbridge, citizens formed an organization, Madeira Beach United, to oppose ... and change the small town center to a high rise urban environment. , According ...
(Date:5/26/2016)... ... 2016 , ... According to the Webster’s dictionary, a hippie is defined as ... one company is going against the norm with a line of all-natural skincare that’s ... the green space is proud to announce its latest retail partnership with the Vitamin ...
(Date:5/26/2016)... California (PRWEB) , ... May 26, 2016 , ... ... Barbara this Memorial Day weekend to host their second pop-up shop for three ... Diego fashion forward brand to the Santa Barbara community, a community full of ...
(Date:5/26/2016)... Malvern, PA (PRWEB) , ... May 26, 2016 ... ... Sharon Wolf has been hired as FluidEdge’s Vice President of Business Intelligence and ... health analytics, Wolf has demonstrated success leading teams as a healthcare business and ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... May 25, 2016 Digital Health Dialog, ... it by the US Patent and Trademark Office ... includes proprietary processes for electronic opt-­in and processing ... wellness programs, HIPAA compliance and otherwise. ... "Our technology allows for individuals ...
(Date:5/24/2016)... , May 24, 2016 ... den Markt gebracht, die es Ärzten erlaubt, ihre ... zu behandeln: MDLinking kombiniert Live Streaming mit einer ... Umfeld zu kommunizieren. Mediziner in Europa, Afrika, Asien ... sich bereits für die Plattform registriert. ...
(Date:5/24/2016)... , May 24, 2016  Diana Russell suffers ... her organs from the inside out.  This disease has ... dependent on her children and grandchildren to leave her ... wheelchair, Diana,s family cannot haul the wheelchair.  So if ... the car, and Diana is left to wait for ...
Breaking Medicine Technology: