Department: Neurosurgery

E-mail: randy.jensen@hsc.utah.edu
Address: 4342 HCI
Phone: 581-6550

Research Title: Calcium Channel Antagonists Potentiate Chemotherapeutic Growth Inhibition of Meningiomas Using a Novel Luciferase Expression Intracranial Mouse Model

Research Description:

Meningiomas are one of the most common primary adult brain tumors.  Although generally thought of as benign, slow growing tumor, meningiomas can have a high degree of morbidity if left untreated or when recurrent after failed therapies.  The primary method of treatment for meningioma is complete surgical resection.   However, many times complete tumor resection is not possible due to the location of the tumor, or because of the inherent biology of some of these tumors there is a high degree of recurrence.  Chemo and radiotherapeutic strategies have also been employed but have not proven very effective. Several novel treatment strategies have been recently developed in our laboratory that show promising results.  Particularly the co-treatment of meningiomas in a subcutanaeous flank mouse model using the calcium channel antagonists Diltiazem and Verapamil with the traditional drug regimens hydroxyurea (HU) and antiprogesterone mifepristone (RU486). We have shown decreasing tumor size, decreasing microvascular density and inducing apoptosis in the G1 phase of the cell cycle after treatment with this combination therapy.   Due to the nature of the blood brain barrier, many drugs that have been quite successful outside of the central nervous system (CNS) have failed in their treatment capabilities in the CNS.  Although the above stated treatment strategies have shown promising results extracranially, it is necessary to test these drugs in an animal model that more closely represents the natural state in which meningiomas occur, namely in an intracranial mouse tumor model.

Our previous work has been in a flank model, in which serial measurement of tumor growth is quite simple. The measurement of tumor growth has proven difficult in intracranial mouse tumor models.  Using mouse MRI to measure tumor size is possible although these techniques are difficult, expensive and time consuming.  Recently we have developed an intracranial mouse model using cell lines stabley transfected with  a luciferase reporter has proven to reliably and accurately measure tumor growth in an in vivo, intracranial model of meningioma.

We propose using this luciferase based intracranial meningioma mouse model to determine the efficacy of the drug regimen consisting of the calcium channel antagonists Diltiazem and Verapamil with RU486 and HU in treating meningioma.

Does this research involve human subjects or animals? Yes

If yes, what is the protocol number? IRB 00014438 and 00014816 and 00034290

10/2009