Nan-fu Chen

Glioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains <30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the activity of chemotherapy drugs. Usually, glutathione S-transferase (GST) superfamily members act as detoxification enzymes by activating xenobiotic metabolites through conjugation with glutathione in healthy cells. However, some overexpressed GSTs not only increase GST activity but also trigger chemotherapy resistance and tumorigenesis-related signaling transductions. Whether GSTM3 is involved in GBM chemoresistance remains unclear. In the current study, we found that T98G, a GBM cell line with pre-existing temozolomide (TMZ) resistance, has high glycolysis and GSTM3 expression. GSTM3 knockdown in T98G decreased glycolysis ability through lactate dehydrogenase A activity reduction. Moreove...

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in...

Platelet-rich plasma (PRP) is prepared by centrifuging fresh blood in an anticoagulant state, and harvesting the platelet-rich portion or condensing platelets. Studies have consistently demonstrated that PRP concentrates are an abundant source of growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), and epithelial growth factor (EGF). The complex mechanisms underlying spinal cord injury (SCI) diminish intrinsic repair and neuronal regeneration. Several studies have suggested that growth factor-promoted axonal regeneration can occur for an extended period after injury. More importantly, the delivery of exogenous growth factors contained in PRP, such as EGF, IGF-1, and TGF-β, has neurotrophic effects on central nervous system (CNS) injuries and neurodegenerative diseases. However, only a few studies have investigated the effects of PRP on CNS injuries or neurodegenerative diseases. According to our re...

Transforming growth factor-βs (TGF-βs) are a group of multifunctional proteins that have neuroprotective roles in various experimental models. We previously reported that intrathecal (i.t.) injections of TGF-β1 significantly inhibit neuropathy-induced thermal hyperalgesia, spinal microglia and astrocyte activation, as well as upregulation of tumor necrosis factor-α. However, additional cellular mechanisms for the antinociceptive effects of TGF-β1, such as the mitogen-activated protein kinase (MAPK) pathway, have not been elucidated. During persistent pain, activation of MAPKs, especially p38 and extracellular signal-regulated kinase (ERK), have crucial roles in the induction and maintenance of pain hypersensitivity, via both nontranscriptional and transcriptional regulation. In the present study, we used a chronic constriction injury (CCI) rat model to explore the role of spinal p38 and ERK in the analgesic effects of TGF-β1. We investigated the cellular mechanisms of the antinocice...

To date, no reliable methods have proven effective for treating spinal cord injury (SCI). Even systemic administration of methylprednisolone (MP) remains controversial. We previously reported that intrathecal (i.t.) administration of granulocyte colony-stimulating factor (G-CSF) improves outcome after experimental spinal cord ischemic insults in rats. The present study aimed to examine the neuroprotective efficacy of i.t. G-CSF or MP in rats with SCI. Female rats were subjected to spinal cord contusion injury at T10 using NYU impactor. We i.t. administered G-CSF (10 μg) or MP (one bolus of 100 μg, followed by 18 μg/h infusion for 23 h) immediately after SCI. Both G-CSF and MP significantly improved the rats' motor function after SCI. Immunofluorescence staining revealed suppressed expression of transforming growth factor-beta 1 (TGF-β1), chondroitin sulfate proteoglycans (neurocan and phosphacan), OX-42 and tumor necrosis factor alpha after i.t. G-CSF, but not MP, in rats with S...

... In the third phase, stability is regained by disc collapse, osteochondrosis, spondylophytes, and locking of the facets 41 . We attempt to use Percudyn to alter the late first phase and cover all mechanical aspects of the second phase of degenerative disc disease. ...

Radiographic study. More detailed anatomical knowledge of the C2 pedicle is required to optimize and minimize the risk of screw placement. The aim of this study was to evaluate the linear and angular dimensions of the true C2 pedicle using axial computed tomography. Although earlier studies have analyzed the anatomy of the C2 pars interarticularis, little attention has been focused on the dimensions of the C2 pedicle. Ninety-three patients (47 males, 46 females; mean age 48.4 y) who had previous cervical spinal computed tomography imaging were evaluated for this study. Axial images of the C2 pedicle were selected and the following pedicle parameters were determined: pedicle width (the mediolateral diameter of the pedicle isthmus, perpendicular to the pedicle axis) and pedicle transverse angle (PTA, ie, the angle between the pedicle axis and the midline of the vertebral body). The overall mean pedicle width was 5.8+/-1.2 mm. The mean pedicle width in male patients (6.0+/-1.3 mm) was greater than that in the female patients (5.6+/-1.1 mm). This difference was not found to be statistically significant (P=0.679). The overall mean PTA was 43.9+/-3.9 degrees. The mean PTA in male patients was 43.2+/-3.8 degrees, whereas that in female patients was 44.7+/-3.7 degrees. Given the significant variability in pedicle widths and the need for precise trajectory planning in pedicle cannulation, preoperative planning is absolutely mandatory. A significant percentage of patients have pedicle widths that may not accommodate screw fixation. In addition, the angle of entry into the C2 pedicle must be carefully measured for safe instrumentation at this level.

Previous studies have reported that the intrathecal (i.t.) administration of transforming growth factor β1 (TGF-β1) prevents and reverses neuropathic pain. However, only limited information is available regarding the possible role and effects of spinal TGF-β1 in neuropathic pain. We aimed to investigate the antinociceptive effects of exogenous TGF-β1 on chronic constriction injury (CCI)-induced neuropathic pain in rats. We demonstrated that sciatic nerve injury caused a downregulation of endogenous TGF-β1 levels on the ipsilateral side of the lumbar spinal dorsal gray matter, and that the i.t. administration of TGF-β1 (.01-10 ng) significantly attenuated CCI-induced thermal hyperalgesia in neuropathic rats. TGF-β1 significantly inhibited CCI-induced spinal neuroinflammation, microglial and astrocytic activation, and upregulation of tumor necrosis factor-α. Moreover, i.t. TGF-β1 significantly attenuated the CCI-induced downregulation of glutamate transporter 1, the glutamate aspartate transporter, and the excitatory amino acid carrier 1 on the ipsilateral side. Furthermore, i.t. TGF-β1 significantly decreased the concentrations of 2 excitatory amino acids, aspartate and glutamate, in the spinal dialysates in CCI rats. In summary, we conclude that the mechanisms of the antinociceptive effects of i.t. TGF-β1 in neuropathy may include attenuation of spinal neuroinflammation, attenuation, or upregulation of glutamate transporter downregulation, and a decrease of spinal extracellular excitatory amino acids. Clinically, medical treatment is usually initiated after the onset of intractable pain. Therefore, in the present study, i.t. TGF-β1 was designed to be administered 2 weeks after the establishment of CCI pain. Compared to the continuous TGF-β1 infusion mode, single-dose administration seems more convenient and practical to use.

In this paper, the authors' goal was to demonstrate the clinical and technical nuances of a minimally invasive lateral extracavitary approach (MI-LECA) for thoracic corpectomy and anterior column reconstruction. A cadaveric feasibility study and the subsequent application of this approach in 3 clinical cases are reported. Six procedures were completed in 3 human cadavers. Minimally invasive, extrapleural thoracic corpectomies were performed with the aid of a 24-mm tubular retraction system, using a posterolateral incision and an oblique approach angle. Fluoroscopy and postprocedural CT scanning, using 3D volumetric averaging software, was used to evaluate the degree of bone removal and decompression. Three clinical cases, including a T-11 burst fracture, a T-7 plasmacytoma, and a T4-5 vertebral body (VB) tuberculosis lesion, were treated using the approach. At 6 cadaveric levels, the mean circumferential volumetric decompression was 48% ± 16%, and the mean resection of the VB was 72% ± 13%. The mean change in anterior and posterior vertebral height with expansion of the corpectomy cage was 47 and 61 mm, respectively. There were no violations of the pleura or dura. Pedicle screw reliability was 95.8% (23 of 24 screws) with a single lateral breach. All 3 patients in the clinical cohort had excellent clinical outcomes. There was a single pleural tear requiring chest tube drainage. Operative images and a video clip are provided to illustrate the approach. A minimally invasive lateral extracavitary thoracic corpectomy has the ability to provided excellent spinal cord decompression and VB resection. The procedure can be completed safely and successfully with minimal blood loss and little associated morbidity. This approach has the potential to improve upon established traditional open corridors for posterolateral thoracic corpectomy.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been approved for use in the lumbar spine in conjunction with the lumbar tapered cage. However, off-label use of this osteoinductive agent is observed with anterior fusion applications as well as with both posterior lumbar interbody fusion and transforaminal lumbar interbody fusion (TLIF). Complications using rhBMP-2 in the cervical spine have been reported. Although radiographic evidence of ectopic bone in the lumbar spine has been described following rhBMP-2 use, this finding was not previously believed to be of clinical relevance. This study was a retrospective review of 4 patients who underwent minimally invasive spinal TLIF (MIS-TLIF) in which bone fusion was augmented with rhBMP-2 applied to an absorbable collagen sponge. Case presentations, operative findings, imaging data, and follow-up findings were reviewed. Four cases with delayed symptomatic neural compression following the off-label use of rhBMP-2 with MIS-TLIF were identified. Although previously believed to be only a radiographic finding, the development of ectopic bone following rhBMP-2 use in lumbar fusion can be clinically significant. This paper describes 4 cases of delayed neural compression following MIS-TLIF. The reader should be aware of this potential complication following the off-label use of rhBMP-2 in the lumbar spine.

Spontaneous spinal epidural hematoma (SSEH) represents 0.3% to 0.9% of spinal epidural space-occupying lesions, and most surgeons advocate aggressive and early surgical intervention. In this article, we describe a patient with SSEH with sudden quadriplegia after sit-ups exercise.