R L Jensen1, R D Wurster. 1. Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84112, USA.
Abstract
BACKGROUND: We have previously shown that calcium channel antagonists inhibit in vitro meningioma growth. This study examines the effect of calcium channel antagonists on in vivo xenograft meningioma growth. METHODS: Meningioma cells taken from human patients were mixed with Matrigel and injected into the subcutaneous space in the flank of nude mice. These animals were treated with calcium channel antagonists in their drinking water. Tumor volumes were measured over time; comparison was made between control and treatment groups. Daily weights, average daily water consumption, and serum calcium channel antagonist levels were determined. Comparison of histology and proliferation index was made between control and treatment groups. RESULTS: Diltiazem treatment decreased tumor growth over time compared to control groups. Increased tumor growth inhibition was seen with increasing doses (p > 0.05). Treatment with verapamil had similar effects; however, there are no statistically significant dose dependent decreases in growth with increasing verapamil doses. There were no tumor "cures" or spontaneous regression of tumor in any group including the control groups. Animal daily weight and average daily water consumption was unaffected by increasing calcium channel antagonist doses compared to control groups. Mouse serum drug levels increased with increasing doses of drug in the drinking water of treatment groups (p > 0.05). Histology and proliferative index of treatment groups were similar to control groups. CONCLUSION: Calcium channel antagonists decrease but do not completely inhibit the growth of meningiomas in nude mice. Clinical correlations and potential applications are discussed.
BACKGROUND: We have previously shown that calcium channel antagonists inhibit in vitro meningioma growth. This study examines the effect of calcium channel antagonists on in vivo xenograft meningioma growth. METHODS:Meningioma cells taken from humanpatients were mixed with Matrigel and injected into the subcutaneous space in the flank of nude mice. These animals were treated with calcium channel antagonists in their drinking water. Tumor volumes were measured over time; comparison was made between control and treatment groups. Daily weights, average daily water consumption, and serum calcium channel antagonist levels were determined. Comparison of histology and proliferation index was made between control and treatment groups. RESULTS:Diltiazem treatment decreased tumor growth over time compared to control groups. Increased tumor growth inhibition was seen with increasing doses (p > 0.05). Treatment with verapamil had similar effects; however, there are no statistically significant dose dependent decreases in growth with increasing verapamil doses. There were no tumor "cures" or spontaneous regression of tumor in any group including the control groups. Animal daily weight and average daily water consumption was unaffected by increasing calcium channel antagonist doses compared to control groups. Mouse serum drug levels increased with increasing doses of drug in the drinking water of treatment groups (p > 0.05). Histology and proliferative index of treatment groups were similar to control groups. CONCLUSION: Calcium channel antagonists decrease but do not completely inhibit the growth of meningiomas in nude mice. Clinical correlations and potential applications are discussed.
Authors: Suganth Suppiah; Farshad Nassiri; Wenya Linda Bi; Ian F Dunn; Clemens Oliver Hanemann; Craig M Horbinski; Rintaro Hashizume; Charles David James; Christian Mawrin; Houtan Noushmehr; Arie Perry; Felix Sahm; Andrew Sloan; Andreas Von Deimling; Patrick Y Wen; Kenneth Aldape; Gelareh Zadeh Journal: Neuro Oncol Date: 2019-01-14 Impact factor: 12.300
Authors: Patrícia Domingues; María González-Tablas; Álvaro Otero; Daniel Pascual; Laura Ruiz; David Miranda; Pablo Sousa; Jesús María Gonçalves; María Celeste Lopes; Alberto Orfao; María Dolores Tabernero Journal: Oncotarget Date: 2015-05-10
Authors: Hisham F Bahmad; Darine Daher; Abed A Aljamal; Mohamad K Elajami; Kei Shing Oh; Juan Carlos Alvarez Moreno; Ruben Delgado; Richard Suarez; Ana Zaldivar; Roshanak Azimi; Amilcar Castellano; Robert Sackstein; Robert J Poppiti Journal: J Histochem Cytochem Date: 2021-06-24 Impact factor: 2.479
Authors: Alfonso Dueñas-González; Patricia García-López; Luis Alonso Herrera; Jose Luis Medina-Franco; Aurora González-Fierro; Myrna Candelaria Journal: Mol Cancer Date: 2008-10-23 Impact factor: 27.401
Authors: Wendy J Ingram; Lisa M Crowther; Erica B Little; Ruth Freeman; Ivon Harliwong; Desi Veleva; Timothy E Hassall; Marc Remke; Michael D Taylor; Andrew R Hallahan Journal: Exp Hematol Oncol Date: 2013-10-04