Faculty

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Florence M Hofman, PhD
Professor of Pathology
Pathology
HMR 315 Health Sciences Campus Los Angeles
+1 323 442 1153

Overview

Dr. Hofman's field of expertise is angiogenesis and the blood-brain-barrier in human primary brain tumors and metastatic breast cancer to the brain. Her approach is to functionally characterize the tumor-associated brain endothelial cells because these cells are the target for anti-vascular therapy in cancer. Her laboratory uses both in vitro and in vivo systems to determine the mechanism(s) of chemoresistance. Once it is understood why these cells are resistant to standard of care drugs, they will identify agents which specifically disrupt the tumor vasculature, resulting in eliminating tumor growth.

Publications

Hofman FM, Taylor CR. Immunohistochemistry. Curr Protoc Immunol. 2013; 103:21. 4. 1-21. 4. 26. View in: PubMed

Jhaveri N, Chen TC, Hofman FM. Tumor vasculature and glioma stem cells: Contributions to glioma progression. Cancer Lett. 2016 Oct 1; 380(2):545-51. View in: PubMed

Kushal S, Wang W, Vaikari VP, Kota R, Chen K, Yeh TS, Jhaveri N, Groshen SL, Olenyuk BZ, Chen TC, Hofman FM, Shih JC. Monoamine oxidase A (MAO A) inhibitors decrease glioma progression. Oncotarget. 2016 Mar 22; 7(12):13842-53. View in: PubMed

Jhaveri N, Agasse F, Armstrong D, Peng L, Commins D, Wang W, Rosenstein-Sisson R, Vaikari VP, Santiago SV, Santos T, Chen L, Schönthal AH, Chen TC, Hofman FM. A novel drug conjugate, NEO212, targeting proneural and mesenchymal subtypes of patient-derived glioma cancer stem cells. Cancer Lett. 2016 Feb 28; 371(2):240-50. View in: PubMed

Dong H, Zou M, Bhatia A, Jayaprakash P, Hofman F, Ying Q, Chen M, Woodley DT, Li W. Breast Cancer MDA-MB-231 Cells Use Secreted Heat Shock Protein-90alpha (Hsp90a) to Survive a Hostile Hypoxic Environment. Sci Rep. 2016; 6:20605. View in: PubMed

Rosa AI, Grade S, Santos SD, Bernardino L, Chen TC, Relvas J, Hofman FM, Agasse F. Heterocellular Contacts with Mouse Brain Endothelial Cells Via Laminin and a6ß1 Integrin Sustain Subventricular Zone (SVZ) Stem/Progenitor Cells Properties. Front Cell Neurosci. 2016; 10:284. View in: PubMed

Schijns VE, Pretto C, Devillers L, Pierre D, Hofman FM, Chen TC, Mespouille P, Hantos P, Glorieux P, Bota DA, Stathopoulos A. First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity. Vaccine. 2015 May 28; 33(23):2690-6. View in: PubMed

Chen TC, Cho HY, Wang W, Nguyen J, Jhaveri N, Rosenstein-Sisson R, Hofman FM, Schönthal AH. A novel temozolomide analog, NEO212, with enhanced activity against MGMT-positive melanoma in vitro and in vivo. Cancer Lett. 2015 Mar 28; 358(2):144-51. View in: PubMed

Wang W, Sivakumar W, Torres S, Jhaveri N, Vaikari VP, Gong A, Howard A, Golden EB, Louie SG, Schönthal AH, Hofman FM, Chen TC. Effects of convection-enhanced delivery of bevacizumab on survival of glioma-bearing animals. Neurosurg Focus. 2015 Mar; 38(3):E8. View in: PubMed

Golden EB, Cho HY, Hofman FM, Louie SG, Schönthal AH, Chen TC. Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors. Neurosurg Focus. 2015 Mar; 38(3):E12. View in: PubMed

Huang TT, Parab S, Burnett R, Diago O, Ostertag D, Hofman FM, Espinoza FL, Martin B, Ibañez CE, Kasahara N, Gruber HE, Pertschuk D, Jolly DJ, Robbins JM. Intravenous administration of retroviral replicating vector, toca 511, demonstrates therapeutic efficacy in orthotopic immune-competent mouse glioma model. Hum Gene Ther. 2015 Feb; 26(2):82-93. View in: PubMed

Chen TC, Cho HY, Wang W, Wetzel SJ, Singh A, Nguyen J, Hofman FM, Schönthal AH. Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo. J Biomed Sci. 2015; 22(1):71. View in: PubMed

Golden EB, Cho HY, Jahanian A, Hofman FM, Louie SG, Schönthal AH, Chen TC. Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy. Neurosurg Focus. 2014 Dec; 37(6):E12. View in: PubMed

Cho HY, Wang W, Jhaveri N, Lee DJ, Sharma N, Dubeau L, Schönthal AH, Hofman FM, Chen TC. NEO212, Temozolomide Conjugated to Perillyl Alcohol, Is a Novel Drug for Effective Treatment of a Broad Range of Temozolomide-Resistant Gliomas. Mol Cancer Ther. 2014 Aug; 13(8):2004-17. View in: PubMed

Chen TC, Cho HY, Wang W, Barath M, Sharma N, Hofman FM, Schönthal AH. A Novel Temozolomide-Perillyl Alcohol Conjugate Exhibits Superior Activity against Breast Cancer Cells In Vitro and Intracranial Triple-Negative Tumor Growth In Vivo. Mol Cancer Ther. 2014 May; 13(5):1181-93. View in: PubMed

Peterson A, Bansal A, Hofman F, Chen TC, Zada G. A systematic review of inhaled intranasal therapy for central nervous system neoplasms: an emerging therapeutic option. J Neurooncol. 2014 Feb; 116(3):437-46. View in: PubMed

Santos T, Fang X, Chen MT, Wang W, Ferreira R, Jhaveri N, Gundersen M, Zhou C, Pagnini P, Hofman FM, Chen TC. Sequential administration of carbon nanotubes and near-infrared radiation for the treatment of gliomas. Front Oncol. 2014; 4:180. View in: PubMed

Ferreira R, Santos T, Amar A, Tahara SM, Chen TC, Giannotta SL, Hofman FM. MicroRNA-18a Improves Human Cerebral Arteriovenous Malformation Endothelial Cell Function. Stroke. 2014 Jan; 45(1):293-7. View in: PubMed

Ferreira R, Santos T, Amar A, Gong A, Chen TC, Tahara SM, Giannotta SL, Hofman FM. Argonaute-2 Promotes miR-18a Entry in Human Brain Endothelial Cells. J Am Heart Assoc. 2014; 3(3). View in: PubMed

Thomas S, Sharma N, Gonzalez R, Pao PW, Hofman FM, Chen TC, Louie SG, Pirrung MC, Schönthal AH. Repositioning of Verrucosidin, a purported inhibitor of chaperone protein GRP78, as an inhibitor of mitochondrial electron transport chain complex I. PLoS One. 2013; 8(6):e65695. View in: PubMed

Sharma N, Thomas S, Golden EB, Hofman FM, Chen TC, Petasis NA, Schönthal AH, Louie SG. Inhibition of autophagy and induction of breast cancer cell death by mefloquine, an antimalarial agent. Cancer Lett. 2012 Dec 30; 326(2):143-54. View in: PubMed

Thomas S, Sharma N, Golden EB, Cho H, Agarwal P, Gaffney KJ, Petasis NA, Chen TC, Hofman FM, Louie SG, Schönthal AH. Preferential killing of triple-negative breast cancer cells in vitro and in vivo when pharmacological aggravators of endoplasmic reticulum stress are combined with autophagy inhibitors. Cancer Lett. 2012 Dec 1; 325(1):63-71. View in: PubMed

Cho HY, Wang W, Jhaveri N, Torres S, Tseng J, Leong MN, Lee DJ, Goldkorn A, Xu T, Petasis NA, Louie SG, Schönthal AH, Hofman FM, Chen TC. Perillyl alcohol for the treatment of temozolomide-resistant gliomas. Mol Cancer Ther. 2012 Nov; 11(11):2462-72. View in: PubMed

Stathopoulos A, Pretto C, Devillers L, Pierre D, Hofman FM, Kruse C, Jadus M, Chen TC, Schijns VE. Development of immune memory to glial brain tumors after tumor regression induced by immunotherapeutic Toll-like receptor 7/8 activation. Oncoimmunology. 2012 May 1; 1(3):298-305. View in: PubMed

Stathopoulos A, Pretto C, Devillers L, Pierre D, Hofman FM, Epstein AL, Farghadani H, Kruse CA, Jadus MR, Chen TC, Schijns VE. Exploring the Therapeutic Efficacy of Glioma Vaccines Based on Allo- and Syngeneic Antigens and Distinct Immunological Costimulation Activators. J Clin Cell Immunol. 2012; Suppl 5:004. View in: PubMed

Jhaveri N, Cho H, Torres S, Wang W, Schönthal AH, Petasis NA, Louie SG, Hofman FM, Chen TC. Noscapine inhibits tumor growth in TMZ-resistant gliomas. Cancer Lett. 2011 Dec 22; 312(2):245-52. View in: PubMed

Stapleton CJ, Armstrong DL, Zidovetzki R, Liu CY, Giannotta SL, Hofman FM. Thrombospondin-1 modulates the angiogenic phenotype of human cerebral arteriovenous malformation endothelial cells. Neurosurgery. 2011 May; 68(5):1342-53; discussion 1353. View in: PubMed

Dong D, Stapleton C, Luo B, Xiong S, Ye W, Zhang Y, Jhaveri N, Zhu G, Ye R, Liu Z, Bruhn KW, Craft N, Groshen S, Hofman FM, Lee AS. A critical role for GRP78/BiP in the tumor microenvironment for neovascularization during tumor growth and metastasis. Cancer Res. 2011 Apr 15; 71(8):2848-57. View in: PubMed

Chen TC, Wang W, Golden EB, Thomas S, Sivakumar W, Hofman FM, Louie SG, Schönthal AH. Green tea epigallocatechin gallate enhances therapeutic efficacy of temozolomide in orthotopic mouse glioblastoma models. Cancer Lett. 2011 Mar 28; 302(2):100-8. View in: PubMed

Wang W, Ghandi A, Liebes L, Louie SG, Hofman FM, Schönthal AH, Chen TC. Effective conversion of irinotecan to SN-38 after intratumoral drug delivery to an intracranial murine glioma model in vivo. Laboratory investigation. J Neurosurg. 2011 Mar; 114(3):689-94. View in: PubMed

Schönthal AH, Chen TC, Hofman FM, Louie SG, Petasis NA. Preclinical development of novel anti-glioma drugs targeting the endoplasmic reticulum stress response. Curr Pharm Des. 2011; 17(23):2428-38. View in: PubMed

Hofman FM, Stathopoulos A, Kruse CA, Chen TC, Schijns VE. Immunotherapy of malignant gliomas using autologous and allogeneic tissue cells. Anticancer Agents Med Chem. 2010 Jul; 10(6):462-70. View in: PubMed

Virrey JJ, Liu Z, Cho HY, Kardosh A, Golden EB, Louie SG, Gaffney KJ, Petasis NA, Schönthal AH, Chen TC, Hofman FM. Antiangiogenic activities of 2,5-dimethyl-celecoxib on the tumor vasculature. Mol Cancer Ther. 2010 Mar; 9(3):631-41. View in: PubMed

Virrey JJ, Golden EB, Sivakumar W, Wang W, Pen L, Schönthal AH, Hofman FM, Chen TC. Glioma-associated endothelial cells are chemoresistant to temozolomide. J Neurooncol. 2009 Oct; 95(1):13-22. View in: PubMed

Cho HY, Thomas S, Golden EB, Gaffney KJ, Hofman FM, Chen TC, Louie SG, Petasis NA, Schönthal AH. Enhanced killing of chemo-resistant breast cancer cells via controlled aggravation of ER stress. Cancer Lett. 2009 Sep 8; 282(1):87-97. View in: PubMed

Zandian M, Belisle R, Mott KR, Nusinowitz S, Hofman FM, Ghiasi H. Optic neuritis in different strains of mice by a recombinant HSV-1 expressing murine interleukin-2. Invest Ophthalmol Vis Sci. 2009 Jul; 50(7):3275-82. View in: PubMed

Jabbour MN, Elder JB, Samuelson CG, Khashabi S, Hofman FM, Giannotta SL, Liu CY. Aberrant angiogenic characteristics of human brain arteriovenous malformation endothelial cells. Neurosurgery. 2009 Jan; 64(1):139-46; discussion 146-8. View in: PubMed

Virrey JJ, Dong D, Stiles C, Patterson JB, Pen L, Ni M, Schönthal AH, Chen TC, Hofman FM, Lee AS. Stress chaperone GRP78/BiP confers chemoresistance to tumor-associated endothelial cells. Mol Cancer Res. 2008 Aug; 6(8):1268-75. View in: PubMed

Virrey JJ, Guan S, Li W, Schönthal AH, Chen TC, Hofman FM. Increased survivin expression confers chemoresistance to tumor-associated endothelial cells. Am J Pathol. 2008 Aug; 173(2):575-85. View in: PubMed

Kardosh A, Golden EB, Pyrko P, Uddin J, Hofman FM, Chen TC, Louie SG, Petasis NA, Schönthal AH. Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib. Cancer Res. 2008 Feb 1; 68(3):843-51. View in: PubMed

Schönthal AH, Chen TC, Hofman FM, Louie SG, Petasis NA. Celecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs. Expert Opin Investig Drugs. 2008 Feb; 17(2):197-208. View in: PubMed

Dong D, Ni M, Li J, Xiong S, Ye W, Virrey JJ, Mao C, Ye R, Wang M, Pen L, Dubeau L, Groshen S, Hofman FM, Lee AS. Critical role of the stress chaperone GRP78/BiP in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor development. Cancer Res. 2008 Jan 15; 68(2):498-505. View in: PubMed

Pyrko P, Schönthal AH, Hofman FM, Chen TC, Lee AS. The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. Cancer Res. 2007 Oct 15; 67(20):9809-16. View in: PubMed

Kardosh A, Soriano N, Pyrko P, Liu YT, Jabbour M, Hofman FM, Schönthal AH. Reduced survivin expression and tumor cell survival during chronic hypoxia and further cytotoxic enhancement by the cyclooxygenase-2 inhibitor celecoxib. J Biomed Sci. 2007 Sep; 14(5):647-62. View in: PubMed

Chen HC, Hofman FM, Kung JT, Lin YD, Wu-Hsieh BA. Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J Virol. 2007 Jun; 81(11):5518-26. View in: PubMed

Dietlin TA, Hofman FM, Lund BT, Gilmore W, Stohlman SA, van der Veen RC. Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion. J Leukoc Biol. 2007 May; 81(5):1205-12. View in: PubMed

Charalambous C, Virrey J, Kardosh A, Jabbour MN, Qazi-Abdullah L, Pen L, Zidovetzki R, Schönthal AH, Chen TC, Hofman FM. Glioma-associated endothelial cells show evidence of replicative senescence. Exp Cell Res. 2007 Apr 1; 313(6):1192-202. View in: PubMed

Gupta V, Su YS, Samuelson CG, Liebes LF, Chamberlain MC, Hofman FM, Schönthal AH, Chen TC. Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas. J Neurosurg. 2007 Mar; 106(3):455-62. View in: PubMed

Milan J, Charalambous C, Elhag R, Chen TC, Li W, Guan S, Hofman FM, Zidovetzki R. Multiple signaling pathways are involved in endothelin-1-induced brain endothelial cell migration. Am J Physiol Cell Physiol. 2006 Jul; 291(1):C155-64. View in: PubMed

Charalambous C, Chen TC, Hofman FM. Characteristics of tumor-associated endothelial cells derived from glioblastoma multiforme. Neurosurg Focus. 2006; 20(4):E22. View in: PubMed

Pyrko P, Soriano N, Kardosh A, Liu YT, Uddin J, Petasis NA, Hofman FM, Chen CS, Chen TC, Schönthal AH. Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC), in tumor cells in vitro and in vivo. Mol Cancer. 2006; 5:19. View in: PubMed

Gupta V, Su YS, Wang W, Kardosh A, Liebes LF, Hofman FM, Schönthal AH, Chen TC. Enhancement of glioblastoma cell killing by combination treatment with temozolomide and tamoxifen or hypericin. Neurosurg Focus. 2006; 20(4):E20. View in: PubMed

Gupta V, Wang W, Sosnowski BA, Hofman FM, Chen TC. Fibroblast growth factor-2-retargeted adenoviral vector for selective transduction of primary glioblastoma multiforme endothelial cells. Neurosurg Focus. 2006; 20(4):E26. View in: PubMed

Kardosh A, Soriano N, Liu YT, Uddin J, Petasis NA, Hofman FM, Chen TC, Schönthal AH. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood. 2005 Dec 15; 106(13):4330-8. View in: PubMed

Charalambous C, Pen LB, Su YS, Milan J, Chen TC, Hofman FM. Interleukin-8 differentially regulates migration of tumor-associated and normal human brain endothelial cells. Cancer Res. 2005 Nov 15; 65(22):10347-54. View in: PubMed

Wu Z, Guo H, Chow N, Sallstrom J, Bell RD, Deane R, Brooks AI, Kanagala S, Rubio A, Sagare A, Liu D, Li F, Armstrong D, Gasiewicz T, Zidovetzki R, Song X, Hofman F, Zlokovic BV. Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nat Med. 2005 Sep; 11(9):959-65. View in: PubMed

Osorio Y, La Point SF, Nusinowitz S, Hofman FM, Ghiasi H. CD8+-dependent CNS demyelination following ocular infection of mice with a recombinant HSV-1 expressing murine IL-2. Exp Neurol. 2005 May; 193(1):1-18. View in: PubMed

Kardosh A, Wang W, Uddin J, Petasis NA, Hofman FM, Chen TC, Schönthal AH. Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-inhibitory function, potently mimics the anti-tumor effects of celecoxib on Burkitt's lymphoma in vitro and in vivo. Cancer Biol Ther. 2005 May; 4(5):571-82. View in: PubMed

Charalambous C, Hofman FM, Chen TC. Functional and phenotypic differences between glioblastoma multiforme-derived and normal human brain endothelial cells. J Neurosurg. 2005 Apr; 102(4):699-705. View in: PubMed

Osorio Y, Cai S, Hofman FM, Brown DJ, Ghiasi H. Involvement of CD8+ T-cells in exacerbation of corneal scarring in mice. Curr Eye Res. 2004 Aug-Sep; 29(2-3):145-51. View in: PubMed

van der Veen RC, Dietlin TA, Karapetian A, Holland SM, Hofman FM. Extra-cellular superoxide promotes T cell expansion through inactivation of nitric oxide. J Neuroimmunol. 2004 Aug; 153(1-2):183-9. View in: PubMed

van der Veen RC, Dietlin TA, Hofman FM. Tissue expression of inducible nitric oxide synthase requires IFN-gamma production by infiltrating splenic T cells: more evidence for immunosuppression by nitric oxide. J Neuroimmunol. 2003 Dec; 145(1-2):86-90. View in: PubMed

Wu Z, Hofman FM, Zlokovic BV. A simple method for isolation and characterization of mouse brain microvascular endothelial cells. J Neurosci Methods. 2003 Nov 30; 130(1):53-63. View in: PubMed

Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, Welch D, Manness L, Lin C, Yu J, Zhu H, Ghiso J, Frangione B, Stern A, Schmidt AM, Armstrong DL, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic B. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med. 2003 Jul; 9(7):907-13. View in: PubMed

Giri R, Selvaraj S, Miller CA, Hofman F, Yan SD, Stern D, Zlokovic BV, Kalra VK. Effect of endothelial cell polarity on beta-amyloid-induced migration of monocytes across normal and AD endothelium. Am J Physiol Cell Physiol. 2002 Sep; 283(3):C895-904. View in: PubMed

Hofman F. Immunohistochemistry. Curr Protoc Immunol. 2002 Aug; Chapter 21:Unit 21. 4. View in: PubMed

Chen TC, Wadsten P, Su S, Rawlinson N, Hofman FM, Hill CK, Schönthal AH. The type IV phosphodiesterase inhibitor rolipram induces expression of the cell cycle inhibitors p21(Cip1) and p27(Kip1), resulting in growth inhibition, increased differentiation, and subsequent apoptosis of malignant A-172 glioma cells. Cancer Biol Ther. 2002 May-Jun; 1(3):268-76. View in: PubMed

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