Nam D Tran

Moffitt Cancer Center, Tampa, Florida, United States

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Publications (10)29.01 Total impact

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    ABSTRACT: Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA and they also express neurotrophins NGF, BDNF and NT3. Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling and neurotrophin signaling is sufficient for long-term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma. Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 12/2014; 290(6). DOI:10.1074/jbc.M114.599373 · 4.57 Impact Factor
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    ABSTRACT: The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.
    Journal of the National Comprehensive Cancer Network: JNCCN 11/2014; 12(11):1517-23. · 4.24 Impact Factor
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    ABSTRACT: Spinal metastatic lesions are a common occurrence among oncology patients and contribute to significant morbidity. Treatment options have been limited in their effectiveness and scope to this point.
    Pain physician 07/2014; 17(4):317-327. · 4.77 Impact Factor
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    ABSTRACT: The development of brain metastases is common in patients with melanoma and is associated with a poor prognosis. Treating patients with melanoma brain metastases (MBMs) is a major therapeutic challenge. Standard approaches with conventional chemotherapy are disappointing, while surgery and radiotherapy have improved outcomes. In this article, we discuss the biology of MBMs, briefly outline current treatment approaches, and emphasize novel and emerging therapies for MBMs. The mechanisms that underlie the metastases of melanoma to the brain are unknown; therefore, it is necessary to identify pathways to target MBMs. Most patients with MBMs have short survival times. Recent use of immune-based and targeted therapies has changed the natural history of metastatic melanoma and may be effective for the treatment of patients with MBMs. Developing a better understanding of the factors responsible for MBMs will lead to improved management of this disease. In addition, determining the optimal treatments for MBMs and how they can be optimized or combined with other therapies, along with appropriate patient selection, are challenges for the management of this disease.
    Cancer control: journal of the Moffitt Cancer Center 10/2013; 20(4):298-306. · 2.66 Impact Factor
  • Nam D. Tran · Bassem A. Georgy
    The Spine Journal 09/2013; 13(9):S165-S166. DOI:10.1016/j.spinee.2013.07.416 · 2.80 Impact Factor
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    ABSTRACT: The objective of this study was to compare the stiffness and range of motion (ROM) of 4 cervical spine constructs and the intact condition. The 4 constructs consisted of 3-level anterior cervical discectomy with anterior plating, 1-level discectomy and 1-level corpectomy with anterior plating, 2-level corpectomy with anterior plating, and 2-level corpectomy with anterior plating and posterior fixation. Eight human cadaveric fresh-frozen cervical spines from C2-T2 were used. Three-dimensional motion analysis with an optical tracking device was used to determine motion following various reconstruction methods. The specimens were tested in the following conditions: 1) intact; 2) segmental construct with discectomies at C4-5, C5-6, and C6-7, with polyetheretherketone (PEEK) interbody cage and anterior plate; 3) segmental construct with discectomy at C6-7 and corpectomy of C-5, with PEEK interbody graft at the discectomy level and a titanium cage at the corpectomy level; 4) corpectomy at C-5 and C-6, with titanium cage and an anterior cervical plate; and 5) corpectomy at C-5 and C-6, with titanium cage and an anterior cervical plate, and posterior lateral mass screw-rod system from C-4 to C-7. All specimens underwent a pure moment application of 2 Nm with regards to flexion-extension, lateral bending, and axial rotation. In all tested motions the statistical comparison was significant between the intact condition and the 2-level corpectomy with anterior plating and posterior fixation construct. All other statistical comparisons between the instrumented constructs were not statistically significant except between the 3-level discectomy with anterior plating and the 2-level corpectomy with anterior plating in axial rotation. There were no statistically significant differences between the 1-level discectomy and 1-level corpectomy with anterior plating and the 2-level corpectomy with anterior plating in any tested motion. There was also no statistical significance between the 3-level discectomy with anterior plating and the 2-level corpectomy with anterior plating and posterior fixation. This study demonstrates that segmental plate fixation (3-level discectomy) affords the same stiffness and ROM as circumferential fusion in 2-level cervical spine corpectomy in the immediate postoperative setting. This obviates the need for staged circumferential procedures for multilevel cervical spondylotic myelopathy. Given that the posterior segmental instrumentation confers significant stability to a multilevel cervical corpectomy, the surgeon should strongly consider the placement of segmental posterior instrumentation to significantly improve the overall stability of the fusion construct after a 2-level cervical corpectomy.
    Journal of neurosurgery. Spine 03/2012; 16(6):579-84. DOI:10.3171/2012.2.SPINE11611 · 2.36 Impact Factor
  • Setzer M · Tran N · Vrionis FD
    Handbook of Spine Surgery, 1 edited by A.A. Baaj, P.V. Mummaneni, J.S. Uribe, A.R. Vaccaro und M.S. Greenberg, 01/2012: chapter 37: pages 259-264; Thieme Verlag., ISBN: 978-1-60406-419-3
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    ABSTRACT: Balloon kyphoplasty has recently been shown to be effective in providing rapid pain relief and enhancing health-related quality of life in patients with metastatic spinal tumors. When performed to treat lesions of the upper thoracic spine, kyphoplasty poses certain technical challenges because of the smaller size of the pedicle and vertebral bodies. Fluoroscopic visualization is also difficult due to interference of the shoulder. The authors' objective in the present study was to evaluate their approach and the results of balloon kyphoplasty in the upper thoracic spine in patients with metastatic spinal disease. Fourteen patients underwent kyphoplasty via an extrapedicular approach to treat metastatic tumors in the upper (T1-5) thoracic spine. Electrodiagnostic monitoring (somatosensory and motor evoked potentials) was used in 5 cases. Three levels were treated in 7 cases, 2 levels in 2 cases, and 1 level in 5 cases. In 3 cases access was bilateral, whereas in 11 cases access was unilateral. The procedure took an average of 25 minutes per treated level, and the mean amount of cement applied was 3 ml per level. Four patients were discharged from the hospital on the day of the procedure, and 10 patients went home after 24 hours. All patients exhibited marked improvement in mean visual analog scale scores (preoperative score 79 vs postoperative score 30, respectively) and Oswestry Disability Index scores (83 vs 33, respectively). The mean kyphotic angle was 25.03° preoperatively, whereas the mean postoperative angle was 22.65° (p > 0.3). At latest follow-up, the mean kyphotic angle did not differ significantly from the postoperative kyphotic angle (26.3°, p > 0.1). No neurological deficits or lung-related complications (pneumothorax or hemothorax) were encountered in any of the patients. Polymethylmethacrylate cement extravasations were observed in 3 (10%) of 30 treated vertebral bodies without any sequelae. By a mean follow-up of 16 months, no patients had experienced an adjacent-level fracture. Balloon kyphoplasty of the upper thoracic spine via an extrapedicular approach is an efficient and safe minimally invasive procedure that may provide immediate and long-term pain relief and improvement in functional ability. It is technically challenging and has the potential for serious complications. With a fundamental knowledge of anatomy, as well as an ability to interpret fluoroscopy images, one can feasibly and safely perform balloon kyphoplasty in the upper thoracic spine.
    Journal of neurosurgery. Spine 03/2011; 14(3):372-6. DOI:10.3171/2010.11.SPINE09909 · 2.36 Impact Factor
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    ABSTRACT: Single-stage posterior corpectomy for the management of spinal tumors has been well described. Anterior column reconstruction has been accomplished using polymethylmethacrylate (PMMA) or expandable cages (EC). The aim of this retrospective study was to compare PMMA versus ECs in anterior vertebral column reconstruction after posterior corpectomy for tumors in the lumbar and thoracolumbar spine. Between 2006 and 2009 we identified 32 patients that underwent a single-stage posterior extracavitary tumor resection and anterior reconstruction, 16 with PMMA and 16 with EC. There were no baseline differences in regards to age (mean: 58.2 years) or performance status. Differences between groups in terms of survival, estimated blood loss (EBL), kyphosis reduction (decrease in Cobb's angle), pain, functional outcomes, and performance status were evaluated. Mean overall survival and EBL were 17 months and 1165 ml, respectively. No differences were noted between the study groups in regards to survival (p = 0.5) or EBL (p = 0.8). There was a trend for better Kyphosis reduction in favor of the EC group (10.04 vs. 5.45, p = 0.16). No difference in performance status or VAS improvements was observed (p > 0.05). Seven patients had complications that led to reoperation (5 infections). PMMA or ECs are viable options for reconstruction of the anterior vertebral column following tumor resection and corpectomy. Both approaches allow for correction of the kyphotic deformity, and stabilization of the anterior vertebral column with similar functional and performance status outcomes in the lumbar and thoracolumbar area.
    European Spine Journal 03/2011; 20(8):1363-70. DOI:10.1007/s00586-011-1738-1 · 2.47 Impact Factor
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    ABSTRACT: The vascular supply of the thoracic spinal cord depends on the thoracolumbar segmental arteries. Because of the small size and ventral course of these arteries in relation to the dorsal root ganglion and ventral root, they cannot be reliably identified during surgery by anatomic or morphologic criteria. Sacrificing them will most likely result in paraplegia. The goal of this study was to evaluate a novel method of intraoperative testing of a nerve root's contribution to the blood supply of the thoracic spinal cord. This is a clinical retrospective study of 49 patients diagnosed with thoracic spine tumors. Temporary nerve root clipping combined with motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring was performed; additionally, postoperative clinical evaluation was done and reported in all cases. All cases were monitored by SSEP and MEPs. The nerve root to be sacrificed was temporarily clipped using standard aneurysm clips, and SSEP/MEP were assessed before and after clipping. Four nerve roots were sacrificed in four cases, three nerve roots in eight cases, and two nerve roots in 22 cases. Nerve roots were sacrificed bilaterally in 12 cases. Most patients (47/49) had no changes in MEP/SSEP and had no neurological deficit postoperatively. One case of a spinal sarcoma demonstrated changes in MEP after temporary clipping of the left T11 nerve root. The nerve was not sacrificed, and the patient was neurologically intact after surgery. In another case of a sarcoma, MEPs changed in the lower limbs after ligation of left T9 nerve root. It was felt that it was a global event because of anesthesia. Postoperatively, the patient had complete paraplegia but recovered almost completely after 6 months. Temporary nerve root clipping combined with MEP and SSEP monitoring may enhance the impact of neuromonitoring in the intraoperative management of patients with thoracic spine tumors and favorably influence neurological outcome.
    The spine journal: official journal of the North American Spine Society 05/2010; 10(5):396-403. DOI:10.1016/j.spinee.2010.02.015 · 2.80 Impact Factor

Publication Stats

26 Citations
29.01 Total Impact Points

Institutions

  • 2011–2014
    • Moffitt Cancer Center
      Tampa, Florida, United States
  • 2012
    • Goethe-Universität Frankfurt am Main
      • Institut für Neurochirurgie
      Frankfurt am Main, Hesse, Germany
  • 2010
    • University of South Florida
      • Morsani College of Medicine
      Tampa, Florida, United States