Jaime F. Modiano, VMD, PhD, University Minnesota, Twin Cities

Jaime F. Modiano, VMD, PhD
Jaime F. Modiano, VMD, PhD

The underlying theme in the Modiano Lab is to understand mechanisms of neoplastic transformation and tumor progression. Ongoing projects include studies of: Cancer Biology and Pathogenesis, Novel Approaches for Cancer Immunotherapy, and Lymphocyte Growth Regulation.

The Investigator's Annexe Part of The Investigator's Annexe program.

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References

  1. Scott MC, Sarver AL, Gavin KJ, Thayanithy V, Getzy DM, Newman RA, Cutter GR, Lindblad-Toh K, Kisseberth WC, Hunter LE, Subramanian S, Breen M, Modiano JF. Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach. Bone. 2011 Sep;49(3):356-67. doi: 10.1016/j.bone.2011.05.008. Epub 2011 May 15.
  2. Wells JW, Evans CH, Scott MC, Rütgen BC, O'Brien TD, Modiano JF, Cvetkovic G, Tepic S. Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation. PLoS One. 2013;8(1):e54464. doi: 10.1371/journal.pone.0054464. Epub 2013 Jan 24.
  3. Cannon CM, Pozniak J, Scott MC, Ito D, Gorden BH, Graef AJ, Modiano JF. Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors. Vet Comp Oncol. 2015 Mar;13(1):48-59. doi: 10.1111/vco.12018. Epub 2013 Feb 15.
  4. Wolfe TD, Pillai SP, Hildreth BE 3rd, Lanigan LG, Martin CK, Werbeck JL, Rosol TJ. Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice. Clin Exp Metastasis. 2011 Apr;28(4):377-89. doi: 10.1007/s10585-011-9377-9. Epub 2011 Mar 4.
  5. Modiano JF, Bellgrau D, Cutter GR, Lana SE, Ehrhart NP, Ehrhart E, Wilke VL, Charles JB, Munson S, Scott MC, Pozniak J, Carlson CS, Schaack J, Duke RC. Inflammation, apoptosis, and necrosis induced by neoadjuvant fas ligand gene therapy improves survival of dogs with spontaneous bone cancer. Mol Ther. 2012 Dec;20(12):2234-43. doi: 10.1038/mt.2012.149. Epub 2012 Jul 31.
  6. Fossey SL, Liao AT, McCleese JK, Bear MD, Lin J, Li PK, Kisseberth WC, London CA. Characterization of STAT3 activation and expression in canine and human osteosarcoma.BMC Cancer. 2009 Mar 10;9:81. doi: 10.1186/1471-2407-9-81.
  7. McCleese JK, Bear MD, Fossey SL, Mihalek RM, Foley KP, Ying W, Barsoum J, London CA. The novel HSP90 inhibitor STA-1474 exhibits biologic activity against osteosarcoma cell lines. Int J Cancer. 2009 Dec 15;125(12):2792-801. doi: 10.1002/ijc.24660.
  8. Liao AT, McCleese J, Kamerling S, Christensen J, London CA. A novel small molecule Met inhibitor, PF2362376, exhibits biological activity against osteosarcoma. Vet Comp Oncol. 2007 Sep;5(3):177-96. doi: 10.1111/j.1476-5829.2007.00137.x.
  9. McMahon MB, Bear MD, Kulp SK, Pennell ML, London CA. Biological activity of gemcitabine against canine osteosarcoma cell lines in vitro. Am J Vet Res. 2010 Jul;71(7):799-808. doi: 10.2460/ajvr.71.7.799.
  10. Fossey SL, Bear MD, Lin J, Li C, Schwartz EB, Li PK, Fuchs JR, Fenger J, Kisseberth WC, London CA. The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines. BMC Cancer. 2011 Mar 28;11:112. doi: 10.1186/1471-2407-11-112.
  11. Fossey SL, Bear MD, Kisseberth WC, Pennell M, London CA. Oncostatin M promotes STAT3 activation, VEGF production, and invasion in osteosarcoma cell lines. BMC Cancer. 2011 Apr 11;11:125. doi: 10.1186/1471-2407-11-125.
  12. London CA, Bear MD, McCleese J, Foley KP, Paalangara R, Inoue T, Ying W, Barsoum J. Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer. PLoS One. 2011;6(11):e27018. doi: 10.1371/journal.pone.0027018. Epub 2011 Nov 3.
  13. McCleese JK, Bear MD, Kulp SK, Mazcko C, Khanna C, London CA. Met interacts with EGFR and Ron in canine osteosarcoma. Vet Comp Oncol. 2013 Jun;11(2):124-39. doi: 10.1111/j.1476-5829.2011.00309.x. Epub 2011 Dec 8.
  14. Thayanithy V, Park C, Sarver AL, Kartha RV, Korpela DM, Graef AJ, Steer CJ, Modiano JF, Subramanian S. Combinatorial treatment of DNA and chromatin-modifying drugs cause cell death in human and canine osteosarcoma cell lines. PLoS One. 2012;7(9):e43720. doi: 10.1371/journal.pone.0043720. Epub 2012 Sep 5.
  15. Couto JI, Bear MD, Lin J, Pennel M, Kulp SK, Kisseberth WC, London CA. Biologic activity of the novel small molecule STAT3 inhibitor LLL12 against canine osteosarcoma cell lines. BMC Vet Res. 2012 Dec 17;8:244. doi: 10.1186/1746-6148-8-244.
  16. Lamerato-Kozicki AR, Helm KM, Jubala CM, Cutter GC, Modiano JF. Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation. Exp Hematol. 2006 Jul;34(7):870-8.
  17. Tamburini BA, Trapp S, Phang TL, Schappa JT, Hunter LE, Modiano JF. Gene expression profiles of sporadic canine hemangiosarcoma are uniquely associated with breed. PLoS One. 2009 May 20;4(5):e5549. doi: 10.1371/journal.pone.0005549.
  18. Tamburini BA, Phang TL, Fosmire SP, Scott MC, Trapp SC, Duckett MM, Robinson SR, Slansky JE, Sharkey LC, Cutter GR, Wojcieszyn JW, Bellgrau D, Gemmill RM, Hunter LE, Modiano JF. Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma. BMC Cancer. 2010 Nov 9;10:619. doi: 10.1186/1471-2407-10-619.
  19. Schappa JT, Frantz AM, Gorden BH, Dickerson EB, Vallera DA, Modiano JF. Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors. Int J Cancer. 2013 Oct 15;133(8):1936-44. doi: 10.1002/ijc.28187. Epub 2013 Apr 25.
  20. Stiles JM, Amaya C, Rains S, Diaz D, Pham R, Battiste J, Modiano JF, Kokta V, Boucheron LE, Mitchell DC, Bryan BA. Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma. PLoS One. 2013;8(3):e60021. doi: 10.1371/journal.pone.0060021. Epub 2013 Mar 28.
  21. Gorden BH, Kim JH, Sarver AL, Frantz AM, Breen M, Lindblad-Toh K, O'Brien TD, Sharkey LC, Modiano JF, Dickerson EB. Identification of three molecular and functional subtypes in canine hemangiosarcoma through gene expression profiling and progenitor cell characterization. Am J Pathol. 2014 Apr;184(4):985-95. doi: 10.1016/j.ajpath.2013.12.025. Epub 2014 Feb 11.
  22. Khammanivong A, Gorden BH, Frantz AM, Graef AJ, Dickerson EB. Identification of drug-resistant subpopulations in canine hemangiosarcoma. Vet Comp Oncol. 2014 Aug 11. doi: 10.1111/vco.12114.
  23. Rodriguez AM, Graef AJ, LeVine DN, Cohen IR, Modiano JF, Kim JH. Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma. J Vet Intern Med. 2015 Jul;29(4):1088-97. doi: 10.1111/jvim.13570. Epub 2015 Jun 25.
  24. Fosmire SP, Dickerson EB, Scott AM, Bianco SR, Pettengill MJ, Meylemans H, Padilla M, Frazer-Abel AA, Akhtar N, Getzy DM, Wojcieszyn J, Breen M, Helfand SC, Modiano JF. Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium. Lab Invest. 2004 May;84(5):562-72.
  25. Frazer-Abel AA, Baksh S, Fosmire SP, Willis D, Pierce AM, Meylemans H, Linthicum DS, Burakoff SJ, Coons T, Bellgrau D, Modiano JF. Nicotine activates nuclear factor of activated T cells c2 (NFATc2) and prevents cell cycle entry in T cells. J Pharmacol Exp Ther. 2004 Nov;311(2):758-69. Epub 2004 Jul 1.
  26. Dickerson EB, Thomas R, Fosmire SP, Lamerato-Kozicki AR, Bianco SR, Wojcieszyn JW, Breen M, Helfand SC, Modiano JF. Mutations of phosphatase and tensin homolog deleted from chromosome 10 in canine hemangiosarcoma. Vet Pathol. 2005 Sep;42(5):618-32.
  27. Kim JH, Frantz AM, Anderson KL, Graef AJ, Scott MC, Robinson S, Sharkey LC, O'Brien TD, Dickerson EB, Modiano JF. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment. Exp Cell Res. 2014 Apr 15;323(1):155-64. doi: 10.1016/j.yexcr.2014.02.020. Epub 2014 Feb 25.
  28. Gorden BH, Saha J, Khammanivong A, Schwartz GK, Dickerson EB. Lysosomal drug sequestration as a mechanism of drug resistance in vascular sarcoma cells marked by high CSF-1R expression. Vasc Cell. 2014 Oct 1;6:20. doi: 10.1186/2045-824X-6-20. eCollection 2014.
  29. Bianco SR, Sun J, Fosmire SP, Hance K, Padilla ML, Ritt MG, Getzy DM, Duke RC, Withrow SJ, Lana S, Matthiesen DT, Dow SW, Bellgrau D, Cutter GR, Helfand SC, Modiano JF. Enhancing antimelanoma immune responses through apoptosis. Cancer Gene Ther. 2003 Sep;10(9):726-36.
  30. Milner RJ, Salute M, Crawford C, Abbot JR, Farese J. The immune response to disialoganglioside GD3 vaccination in normal dogs: a melanoma surface antigen vaccine. Vet Immunol Immunopathol. 2006 Dec 15;114(3-4):273-84. Epub 2006 Oct 5.
  31. Igase M, Hwang CC, Coffey M, Okuda M, Noguchi S, Mizuno T. The oncolytic effects of reovirus in canine solid tumor cell lines. J Vet Med Sci. 2015 Jun 1;77(5):541-8. doi: 10.1292/jvms.14-0570. Epub 2015 Jan 16.
  32. Enjoji S, Yabe R, Fujiwara N, Tsuji S, Vitek MP, Mizuno T, Nakagawa T, Usui T, Ohama T, Sato K. The therapeutic effects of SET/I2PP2A inhibitors on canine melanoma. J Vet Med Sci. 2015 Jun 11.
  33. Ritt MG, Wojcieszyn J, Modiano JF. Functional loss of p21/Waf-1 in a case of benign canine multicentric melanoma. Vet Pathol. 1998 Mar;35(2):94-101.
  34. Modiano JF, Ritt MG, Wojcieszyn J, Smith R 3rd. Growth arrest of melanoma cells is differentially regulated by contact inhibition and serum deprivation. DNA Cell Biol. 1999 May;18(5):357-67.
  35. Ritt MG, Mayor J, Wojcieszyn J, Smith R, Barton CL, Modiano JF. Sustained nuclear localization of p21/WAF-1 upon growth arrest induced by contact inhibition. Cancer Lett. 2000 Sep 29;158(1):73-84.
  36. Koenig A, Wojcieszyn J, Weeks BR, Modiano JF. Expression of S100a, vimentin, NSE, and melan A/MART-1 in seven canine melanoma cells lines and twenty-nine retrospective cases of canine melanoma. Vet Pathol. 2001 Jul;38(4):427-35.
  37. Koenig A, Bianco SR, Fosmire S, Wojcieszyn J, Modiano JF. Expression and significance of p53, rb, p21/waf-1, p16/ink-4a, and PTEN tumor suppressors in canine melanoma. Vet Pathol. 2002 Jul;39(4):458-72.
  38. Kim JH, Frantz AM, Anderson KL, Graef AJ, Scott MC, Robinson S, Sharkey LC, O'Brien TD, Dickerson EB, Modiano JF. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment. Exp Cell Res. 2014 Apr 15;323(1):155-64.
  39. Murahari S, Jalkanen AL, Kulp SK, Chen CS, Modiano JF, London CA, Kisseberth WC. Sensitivity of osteosarcoma cells to HDAC inhibitor AR-42 mediated apoptosis. BMC Cancer. 2017 Jan 21;17(1):67. doi: 10.1186/s12885-017-3046-6. PubMed PMID: 28109246; PubMed Central PMCID: PMC5251323.
  40. Scott MC, Tomiyasu H, Garbe JR, Cornax I, Amaya C, O'Sullivan MG, Subramanian S, Bryan BA, Modiano JF. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior. Dis Model Mech. 2016 Dec 1;9(12):1435-1444. Epub 2016 Nov 3. PubMed PMID: 27874835; PubMed Central PMCID: PMC5200896.
  41. Fenger JM, Roberts RD, Iwenofu OH, Bear MD, Zhang X, Couto JI, Modiano JF, Kisseberth WC, London CA. MiR-9 is overexpressed in spontaneous canine osteosarcoma and promotes a metastatic phenotype including invasion and migration in osteoblasts and osteosarcoma cell lines. BMC Cancer. 2016 Oct 10;16(1):784. PubMed PMID: 27724924; PubMed Central PMCID: PMC5057229.
  42. Scott MC, Sarver AL, Tomiyasu H, Cornax I, Van Etten J, Varshney J, O'Sullivan MG, Subramanian S, Modiano JF. Aberrant Retinoblastoma (RB)-E2F Transcriptional Regulation Defines Molecular Phenotypes of Osteosarcoma. J Biol Chem. 2015 Nov 20;290(47):28070-83. doi: 10.1074/jbc.M115.679696. Epub 2015 Sep 16. PubMed PMID: 26378234; PubMed Central PMCID: PMC4653667.
  43. Im KS, Graef AJ, Breen M, Lindblad-Toh K, Modiano JF, Kim JH. Interactions between CXCR4 and CXCL12 promote cell migration and invasion of canine hemangiosarcoma. Vet Comp Oncol. 2017 Jun;15(2):315-327. doi: 10.1111/vco.12165. Epub 2015 Sep 3. PubMed PMID: 26337509.
  44. Lin W, Modiano JF, Ito D. Stage-specific embryonic antigen: determining expression in canine glioblastoma, melanoma, and mammary cancer cells. J Vet Sci. 2017 Mar 30;18(1):101-104. doi: 10.4142/jvs.2017.18.1.101. PubMed PMID: 27456773; PubMed Central PMCID: PMC5366293.