title: Multi-Scale Agent-Based Multiple Myeloma Cancer Modeling and the Related Study of the Balance between Osteoclasts and Osteoblasts.
abstract: BACKGROUND
  Currently, multiple myeloma is the second most common hematological malignancy in the U.S., constituting 1% of all cancers. With conventional treatment, the median survival time is typically 3-4 years, although it can be extended to 5-7 years or longer with advanced treatments. Recent research indicated that an increase in osteoclast (OC) activity is often associated withmultiple myeloma (MM) and that a decrease inosteoblast (OB) activity contributesto the osteolytic lesions in MM. Normally, the populations of OCs and OBs are inequilibrium, and an imbalance in this statecontributes to the development of lesions.
  A multi-scale agent-based multiple myeloma model was developed to simulate the proliferation, migration and death of OBs and OCs. Subsequently, this model was employed to investigate the efficacy of thethree most commonly used drugs for MM treatment under the following two premises: the reduction in the progression of MM and the re-establishment of the equilibrium between OCs and OBs.
  The simulated results not only demonstrated the capacity of the model to choose optimal combinations of the drugs but also showed that the optimal use of the three drugs can restore the balance between OCs and OBs as well as kill MMs. Furthermore, the drug synergism analysis function of the model revealed that restoring the balance between OBs and OCs can significantly increase the efficacy of drugs against tumor cells.
authors.affiliation: College of Computer and Information Science, Southwest University, Chongqing, P. R. China.
authors.forename: Minna
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Department of Radiology, Wake Forest University School of Medicine, Winston Salem, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Carey
authors.affiliation: Department of Radiology, Wake Forest University School of Medicine, Winston Salem, United States of America.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
authors.affiliation: College of Computer and Information Science, Southwest University, Chongqing, P. R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000617:Aminoglycosides / Q000493:pharmacokinetics / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053281:Enediynes / Q000493:pharmacokinetics / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D015233:Models, Statistical; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C501126:DKK1 protein, human; D053281:Enediynes; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; C058024:C 1027; C557618:BHQ880