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UF Health University of Florida
David Tran Laboratory of Quantitative Cancer Research Department of Neurosurgery in the College of Medicine

Publications

Featured Publications

Radiographic appearances of post-LITT changes

Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier

Eric C. Leuthardt, Chong Duan, Michael J. Kim, Jian L. Campian, Albert H. Kim, Michelle M. Miller-Thomas, Joshua S. Shimony, and David D. Tran* (2015)
*Senior/corresponding author

Plos One. 11(2):e0148613

Poor central nervous system penetration of cytotoxic drugs due to the blood brain barrier (BBB) is a major limiting factor in the treatment of brain tumors. Most recurrent glioblastomas (GBM) occur within the peritumoral region. In this study, we describe a hyperthemic method to induce temporary disruption of the peritumoral BBB that can potentially be used to enhance drug delivery.

This study was one of the top 1% most downloaded articles in PlosOn and was the subject of a Reddit Science AMA (Ask Me Anything).

Cancer Metastais illustration

Temporal and Spatial Cooperation of Snail1 and Twist1 During Epithelial-mesenchymal Transition Predicts for Human Breast Cancer Recurrence

David D. Tran*, Callie Ann S. Corsa, Hirak Biswas, Rebecca L. Aft, and Gregory D. Longmore (2011)
*Senior/corresponding author

Mol Cancer Res. 2011 Dec; 9(12): 1644–1657

Cancer metastasis remains the leading cause of cancer mortality. The metastatic process has been shown to share many parallels with epithelial–mesenchymal transition (EMT), a normal and reversible morphogenetic program that facilitates cell movements during development. In both developmental and cancer EMT, signals initiating and regulating this process emanate from the tissue microenvironment and include TGFβ, Wnt, hepatocyte growth factor (HGF), epidermal growth factor (EGF), and hypoxia.

To determine why cancer cells concurrently express multiple EMT inducers, we determined and contrasted the endogenous expression patterns of several EMT-inducing factors in multiple human epithelial and carcinoma cell lines.

This study was a featured free article in the Molecular Cancer Research journal in the December 2011 issue.

Effect of TumoKaplan-Meier Survival Curves for Patients Included in the Final Analysis in the Intent-to-Treat PopulationKaplan-Meier Survival Curves for Patients Included in the Final Analysis in the Intent-to-Treat PopulationKaplan-Meier Survival Curves for Patients Included in the Final Analysis in the Intent-to-Treat PopulationKaplan-Meier Survival Curves for Patients Included in the Final Analysis in the Intent-to-Treat PopulationKaplan-Meier Survival Curves for Patients Included in the Final Analysis in the Intent-to-Treat PopulationKaplan-Meier Survival Curves for Patients Included in the Final Analysis in the Intent-to-Treat Populationr-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial

Roger Stupp, Sophie Taillibert, Andrew Kanner, William Read, David M. Steinberg, Benoit Lhermitte, Steven Toms, Ahmed Idbaih, Manmeet S. Ahluwalia, Karen Fink, Francesco Di Meco, Frank Lieberman, Jay-Jiguang Zhu, Giuseppe Stragliotto, David D. Tran, Steven Brem, Andreas F. Hottinger, Eilon D. Kirson, Gitit Lavy-Shahaf, Uri Weinberg, Chae-Yong Kim, Sun-Ha Paek, Garth Nicholas, Jordi Burna, Hal Hirte, Michael Weller, Yoram Palti, Monika E. Hegi, and Zvi Ram (2017)

JAMA. 2017;318(23):2306-2316. doi:10.1001/jama.2017.18718

Does the use of tumor-treating fields (TTFields), consisting of low-intensity, alternating electric fields delivered via transducer arrays applied to the scalp, when added to maintenance temozolomide chemotherapy, improve progression-free survival for patients with glioblastoma?

In this randomized clinical trial involving 695 patients with glioblastoma who had completed initial radiochemotherapy, median progression-free survival from randomization was 6.7 months in the TTFields plus temozolomide group and 4.0 months in the temozolomide-alone group (hazard ratio, 0.63), a significant difference.

Among patients with glioblastoma, the addition of TTFields to maintenance temozolomide chemotherapy resulted in statistically significant improvement in survival. These results are consistent with those reported in a previous interim analysis.

Survival Curves for Patients Included in the Interim Analysis in the Intent-to-Treat Population

Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial

Roger Stupp, Sophie Taillibert, Andrew A. Kanner, Santosh Kesari, David M. Steinberg, Steven A. Toms, Lynne P. Taylor, Frank Lieberman, Antonio Silvani, Karen L. Fink, Gene H. Barnett, Jay-Jiguang Zhu, John W. Henson, Herbert H. Engelhard, Thomas C. Chen, David D. Tran, Jan Sroubek, Nam D. Tran, Andreas F. Hottinger, Joseph Landolfi, Rajiv Desai, Manuela Caroli, Yvonne Kew, Jerome Honnorat, Ahmed Idbaih, Eilon D. Kirson, Uri Weinberg, Yoram Palti, Monika E. Hegi, Zvi Ram

JAMA. 2015;314(23):2535-2543. doi:10.1001/jama.2015.16669

Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly.

The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up.

In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival.

SNAIL1 Study Representative Images

Transient SNAIL1 Expression Is Necessary for Metastatic Competence in Breast Cancer

Hung Tran, Krishna Luitel, Michael Kim, Kun Zhang, Gregory Longmore, and David D. Tran*
*Senior/corresponding author

Cancer Res. 2014 Nov 1; 74(21): 6330–6340.

SNAIL1 has been suggested to regulate breast cancer metastasis based on analyses of human breast tumor transcriptomes and experiments using cancer cell lines and xenografts. However, in vivo genetic experimental support for a role for SNAIL1 in breast cancer metastasis that develops in an immunocompetent tumor microenvironment has not been determined. To address this question, we created a genetic SNAIL1 model by coupling an endogenous SNAIL1 reporter with an inducible SNAIL1 transgene.

Using multiple genetic models of breast cancer, we demonstrated that endogenous SNAIL1 expression was restricted to primary tumors that ultimately disseminate. SNAIL1 gene deletion either during the premalignant phase or after primary tumors have reached a palpable size blunted metastasis, indicating that late metastasis was the main driver of metastasis and that this was dependent on SNAIL1. Importantly, SNAIL1 expression during breast cancer metastasis was transient and forced transient, but not continuous. SNAIL1 expression in breast tumors was sufficient to increase metastasis.

All Publications

  1. Jiayi Huang, Jian L Campian, Amit Gujar, Christina Tsien, George Ansstas, David D Tran, Todd A DeWees, A. Craig Lockhart, Albert H Kim (2018). Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma. Neuro-Onc. 138(1): 105-111.
  2. Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran DD, Brem S, Hottinger AF, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Burna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z (2017). Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 318(23):2306-2316. doi: 10.1001/jama.2017.18718.
  3. Mahlokozera T, Vellimana AK, Li T, Mao DD, Zohny ZS, Kim DH, Tran DD, Marcus DS, Fouke SJ, Campian JL, Dunn GP, Miller CA, Kim AH. Biological and therapeutic implications of multisector sequencing in newly diagnosed glioblastomas. Neuro Oncol. 2017 Dec 13. doi: 10.1093/neuonc/nox232. [Epub ahead of print].
  4. Michael Weller, Nicholas Butowski, David D. Tran, Lawrence D. Recht, Michael Lim, Hal Hirte, Lynn Ashby, Lazlo Mechtler, Samuel A. Goldlust, Fabio Iwamoto, Jan Drappatz, Donald M. O’Rourke, Mark Wong, Mark G. Hamilton, Gaetano Finocchiaro, James Perry, Wolfgang Wick, Jennifer Green, Yi He, Christopher D. Turner, Michael J. Yellin, Tibor Keler, Thomas A. Davis, Roger Stupp, and John H. Sampson (2017). Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): results of a randomized, double-blind, international phase 3 trial. Lancet Onc..18(10):1373-1385. doi: 10.1016/S1470-2045(17)30517-X
    1. Correspondence: Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, Drappatz J, O’Rourke DM, Wong M, Hamilton MG, Finocchiaro G, Perry J, Wick W, Green J, He Y, Turner CD, Yellin MJ, Keler T, Davis TA, Stupp R, Sampson JH. Go, no-go decision making for phase 3 clinical trials: ACT IV revisited – Authors’ reply. Lancet Oncol. 2017 Dec;18(12):e709-e710. doi: 10.1016/S1470-2045(17)30856-2.
  5. Kanita Beba Abadal, Meggen A. Walsh, Anthony T. Yachnis, David D. Tran, and Ashley P. Ghiaseddin (2017). Eleven Month Progression–Free Survival on Vemurafenib Monotherapy in a Patient With Recurrent and Metastatic BRAF V600E–Mutated Glioblastoma, WHO Grade 4. JCO Precision Oncology. Published online August 16, 2017.
  6. Andrew Lee Lin, Michael White, Michelle Miller-Thomas, Keith Rich, Christina Tsien, Robert Fulton, Robert Schmidt, David Tran*, and Sonika Dahiya* (2016). Molecular and histologic characteristics of pseudoprogression in diffuse gliomas. J Neurooncol. 130:529. doi:10.1007/s11060-016-2247-1. *Senior/corresponding author.
  7. Amit D Gujar, Son Le, Diane D Mao, David YA Dadey, Alice Turski, Yo Sasaki, Diane Aum, Jingqin Luo, Sonika Dahiya, Liya Yuan, Keith M Rich, Jeffrey Milbrandt, Dennis E Hallahan, Hiroko Yano, David D Tran, Albert H Kim (2016). A NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma. Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):E8247-E8256. doi: 10.1073/pnas.1610921114.
  8. Jiayi Huang, Jian L. Campian, Amit D. Gujar, David D. Tran, A. Craig Lockhart, Todd A. DeWees, Christina I. Tsien, Albert H. Kim (2016). A phase I study to repurpose disulfiram in combination with temozolomide to treat newly diagnosed glioblastoma after chemoradiotherapy. J Neurooncol. 128(2):259-66.
  9. Eric C. Leuthardt, Chong Duan, Michael J. Kim, Jian L. Campian, Albert H. Kim, Michelle M. Miller-Thomas, Joshua S. Shimony, and David D. Tran* (2015). Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier. Plos One. 11(2):e0148613. *Senior/corresponding author.
    1. Selected for Reddit AMA (Ask Me Anything)
    2. Top 1% most downloaded articles in PlosOn
  10. Ansstas G and Tran DD (2016). Treatment with Tumor-Treating Fields Therapy and Pulse Dose Bevacizumab in Patients with Bevacizumab-Refractory Recurrent Glioblastoma: A Case Series. Case Rep Neurol. 8(1)1-9.
  11. Nabors LB, Portnow J, Ammirati M, Baehring J, Brem H, Brown P, Butowski N, Chamberlain MC, Fenstermaker RA, Friedman A, Gilbert MR, Hattangadi-Gluth J, Holdhoff M, Junck L, Kaley T, Lawson R, Loeffler JS, Lovely MP, Moots PL, Mrugala MM, Newton HB, Parney I, Raizer JJ, Recht L, Shonka N, Shrieve DC, Sills AK Jr, Swinnen LJ, Tran D, Tran N, Vrionis FD, Weiss S, Wen PY, McMillian N, Engh AM. Central Nervous System Cancers, Version 1.2015. J Natl Compr Canc Netw. 13(10):1191-1202.
  12. Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 314(23):2535-2543.
  13. Andrei G. Vlassenko, MD, PhD; Jonathan McConathy, MD, PhD; Lars E. Couture, BA; Yi Su, PhD; Parinaz Massoumzadeh, PhD; Hayden S. Leeds; Michael R. Chicoine, MD; David D. Tran, MD; Jiayi Huang, MD; Sonika Dahiya, MD; Daniel S. Marcus, PhD; Sarah Jost Fouke, MD; Keith M. Rich, MD; Marcus E. Raichle, MD; and Tammie LS Benzinger MD, PhD (2015). Aerobic glycolysis in glial human brain tumors. Dis Markers. 2015:874904.
  14. Reardon DA, Schuster JM, Tran DD, Fink KL, Nabors LB, Li G, Bota DA, Lukas RV, Desjardins A, Ashby LS, Duic JP, Mrugala MM, Werner A, Hawthorne T, He Y, Green J, Yellin MJ, Turner CD, Davis TA, Sampson JH (2015. ReACT: Overall Survival From a Randomized Phase II Study of Rindopepimut (CDX-110) Plus Bevacizumab in Relapsed Glioblastoma. Neurosurg. 62, Suppl 1, clinical neurosurgery: 198-199.
  15. Mao DD, Gujar AD, Mahlokozera T, Chen I, Pan Y, Luo J, Brost T, Thompson EA, Turski A, Leuthardt EC, Dunn GP, Chicoine MR, Rich KM, Dowling JL, Zipfel GJ, Dacey RG, Achilefu S, Tran DD, Yano H, Kim AH (2015). A CDC20-APC/SOX signaling axis regulates human glioblastoma stem-like cells. Cell Reports. 11(11):1809-21.
  16. Huang J, DeWees TA, Badiyan SN, Speirs CK, Mullen DF, Fergus S, Tran DD, Linette G, Campian JL, Chicoine MR, Kim AH, Dunn G, Simpson JR, Robinson CG (2015). Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma. Int J Radiat Oncol Biol Phys. 92(5):1000-1007.
  17. Christina K. Speirs, Todd A. DeWees, Joseph R. Simpson, Clifford G. Robinson, David D. Tran, Gerry Linette, Michael R. Chicoine, Ralph G. Dacey, Keith M. Rich, Joshua L. Dowling, Eric C. Leuthardt, Gregory J. Zipfel, Albert H. Kim, Jiayi Huang. (2015). Impact of 1p/19q codeletion and histology on the outcomes of anaplastic gliomas treated with radiotherapy and temozolomide. Int J Rad Onc Biol Phys 91(2):268-276.
  18. Ammar H. Hawasli, Albert H. Kim, Gavin P. Dunn, David D. Tran and Eric C. Leuthardt (2014). Stereotactic Laser Ablation of High-Grade Gliomas. Neurosurg Focus 37(6):E1.
  19. Nabors LB, Portnow J, Ammirati M, Brem H, Brown P, Butowski N, Chamberlain MC, DeAngelis LM, Fenstermaker RA, Friedman A, Gilbert MR, Hattangadi-Gluth J, Hesser D, Holdhoff M, Junck L, Lawson R, Loeffler JS, Moots PL, Mrugala MM, Newton HB, Raizer JJ, Recht L, Shonka N, Shrieve DC, Sills AK Jr, Swinnen LJ, Tran DD, Tran N, Vrionis FD, Wen PY, McMillian NR, Ho M (2014). Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 12(11):1517-1523.
  20. Shahed N Badiyan, Stephanie Markovina, Joseph R Simpson, Clifford G Robinson, Todd DeWees, David D. Tran, Gerry Linette, Rohan Jalalizadeh, Ralph Dacey, Keith M Rich, Michael R Chicoine, Joshua L Dowling, Eric C Leuthardt, Gregory J Zipfel, Albert H Kim, Jiayi Huang (2014). Radiotherapy Dose-Escalation for Glioblastoma Multiforme in the Era of Temozolomide. Int J Rad Onc Biol Phys 90(4):877-885.
  21. Hung Tran, Krishna Luitel, Michael Kim, Kun Zhang, Gregory Longmore, and David D. Tran* (2014). Transient Snail1 Expression is Necessary for Metastatic Competence in Breast Cancer. Cancer Res. 74(21):6330-6340. * Senior/corresponding author.
  22. Maciej M. Mrugala, Herbert H. Engelhard, David D. Tran, Yvonne Kew, Robert Cavaliere, John L. Villano, Daniela Annenelie Bota, Jeremy Rudnick, Ashley Love Sumrall, Jay-Jiguang Zhu, Nicholas Butowski (2014). Clinical Practice Experience With NovoTTF-100A™ System for Glioblastoma: The Patient Registry Dataset (PRiDe). Sem Oncol 41(Supp 6): S4-S13.
  23. Mario E. Lacouture, Mary Elizabeth Davis, Grace Elzinga, Nicholas Butowski, David Tran, John L. Villano, Lucianna DiMeglio, Angela M. Davies, and Eric T. Wong (2014). Characterization and Management of Dermatologic Adverse Events with the NovoTTF™-100A System, a Novel Anti-Mitotic Electric Field Device for the Treatment of Recurrent Glioblastoma (rGB). Semin Oncol 41(Supp 4): S1-S14.
  24. Andrew Lin, Jinxia Liu, John Evans, Eric C. Leuthardt, Keith M.Rich, Ralph G. Dacey, Joshua L. Dowling, Albert H. Kim, Gregory J. Zipfel, Robert L. Grubb, Jiayi Huang, Clifford G. Robinson, Joseph R. Simpson, Gerard P. Linette, Michael Chicoine, and David Tran* (2014). Codeletions at 1p and 19q predict for a lower risk of pseudoprogression in oligodendrogliomas and mixed oligoastrocytomas. Neuro Oncol 16(1): 123-130 *Senior/Corresponding author.
  25. Nabors LB, Ammirati M, Bierman PJ, Brem H, Butowski N, Chamberlain MC, DeAngelis LM, Fenstermaker RA, Friedman A, Gilbert MR, Hesser D, Holdhoff M, Junck L, Lawson R, Loeffler JS, Maor MH, Moots PL, Morrison T, Mrugala MM, Newton HB, Portnow J, Raizer JJ, Recht L, Shrieve DC, Sills AK Jr, Tran DD, Tran N, Vrionis FD, Wen PY, McMillian N, Ho M (2013). Central Nervous System Cancers. J Natl Compr Canc Netw 11(9):1114-1151.
  26. Hawasli AH, Rubin JB, Tran DD, Adkins DR, Waheed S, Hullar TE, Gutmann DH, Evans J, Leonard JR, Zipfel GJ, Chicoine MR (2013). Antiangiogenic agents for nonmalignant brain tumors. J Neurol Surg B Skull Base. 74(3):136-41.
  27. David D. Tran*, Callie Ann S. Corsa, Hirak Biswas, Rebecca L. Aft, and Gregory D. Longmore (2011). Temporal and Spatial cooperation of Snail1 and Twist1 during Epithelial-Mesenchymal Transition predicts for human breast cancer recurrence. Mol Cancer Res 9(12):1644-1657. *D. Tran: Corresponding author. (Free Featured Article).
    1. Editorial highlight: MCR (2011) 9:1571.
  28. Liu Yu, Liviu Malureanu, Jeganathan Karthibabu, David D. Tran, Lonnie Lindquist, Richard J. Bram (2009). CAML loss causes anaphase failure and chromosome missegregation. Cell Cycle 8(6)940-949.
  29. Xu Yuan, Jun Yao, David Norris, David D. Tran, Richard Bram, Gong Chen and Bernhard Luscher (2008). Calcium-modulating cyclophilin ligand regulates membrane trafficking of postsynaptic GABAA Mol. Cell. Neurosci. 38(2)277-289.
  30. David D. Tran, Karen Heckman, David McKean, Jan van Deursen and Richard J. Bram (2005). CAML interacts with p56Lck and is required for T cell development. Immunity 23(8)139-152.
  31. Eugenia Trushina, Roy B. Dyer, John D. Badger II, Daren Ure, Lars Eide, David D. Tran, Brent T. Vrieze, Valerie Legendre-Guillemin, Peter S. McPherson, Bhaskar S. Mandavilli, Bennett Van Houten, Scott Zeitlin, Mark McNiven, Ruedi Aebersold, Michael Hayden, Joseph E. Parisi, Erling Seeberg, Ioannis Dragatsis, Kelly Doyle, Anna Bender, Celin Chacko and Cynthia T. McMurray (2004). Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Cell. Biol. 24(18):8195-8209.
  32. David D. Tran, Helen Russell, Shari L. Sutor, Jan van Deursen and Richard J. Bram (2003). CAML is required for efficient EGF receptor recycling. Developmental Cell 5(2):245-256.
  33. Mary C. Horne, Karen L. Donaldson, Gay Lynn Goolsby, David Tran, Michael Mulheisen, Johannes W. Hell and Alan F. Wahl (1997). Cyclin G2 is up-regulated during growth inhibition and B cell antigen receptor-mediated cell cycle arrest. Biol. Chem. 272: 12650-12661.
  34. Mary C. Horne, Gay Lynn Goolsby, Karen L. Donaldson, David Tran, Michael Neubauer and Alan F. Wahl (1996). Cyclin G1 and Cyclin G2 comprise a new family of cyclins with contrasting tissue-specific and cell cycle-regulated expression. Biol. Chem. 271: 6050-6061.