Repression of multiple myeloma growth and preservation of bone with combined radiotherapy and anti-angiogenic agent.
The effects of ionizing radiation, with or without the anti-angiogenic agent anginex (Ax), on multiple myeloma growth were tested in a SCID-rab mouse model. Mice carrying human multiple myeloma cell-containing pre-implanted bone grafts were treated weekly with various regimens for 8 weeks. Rapid multiple myeloma growth, assessed by bioluminescence intensity (IVIS), human lambda Ig light chain level in serum (ELISA), and the volume of bone grafts (caliper), was observed in untreated mice. Tumor burden in mice receiving combined therapy was reduced to 59% (by caliper), 43% (by ELISA), and 2% (by IVIS) of baseline values after 8 weeks of treatment. Ax or radiation alone slowed but did not stop tumor growth. Four weeks after the withdrawal of the treatments, tumor burden remained minimal in mice given Ax + radiation but increased noticeably in the other three groups. Multiple myeloma suppression by Ax + radiation was accompanied by a marked decrease in the number and activity of osteoclasts in bone grafts assessed by histology. Bone graft integrity was preserved by Ax + radiation but was lost in the other three groups, as assessed by microCT imaging and radiography. These results suggest that radiotherapy, when primed by anti-angiogenic agents, may be a potent therapy for focal multiple myeloma.
Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR72205, USA. jiadan@uams.edu
Dan
D
Jia
Nathan A
NA
Koonce
Roopa
R
Halakatti
Xin
X
Li
Shmuel
S
Yaccoby
Frances L
FL
Swain
Larry J
LJ
Suva
Leah
L
Hennings
Marc S
MS
Berridge
Scott M
SM
Apana
Kevin
K
Mayo
Peter M
PM
Corry
Robert J
RJ
Griffin
D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016025:Bone Transplantation; D001842:Bone and Bones / Q000601:surgery*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D006801:Humans; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D010455:Peptides; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects
D020533:Angiogenesis Inhibitors; D010455:Peptides; D011506:Proteins; D011838:Radiation-Sensitizing Agents; C111993:betapep-25 protein, synthetic