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1.  Low-Level Laser Stimulation on Adipose-Tissue-Derived Stem Cell Treatments for Focal Cerebral Ischemia in Rats 
This study investigated the effects of large-area irradiation from a low-level laser on the proliferation and differentiation of i-ADSCs in neuronal cells. MTT assays indicated no significant difference between the amount of cells with (LS+) and without (LS−) laser treatment (P > 0.05). However, immunofluorescent staining and western blot analysis results indicated a significant increase in the neural stem-cell marker, nestin, following exposure to low-level laser irradiation (P < 0.05). Furthermore, stem cell implantation was applied to treat rats suffering from stroke. At 28 days posttreatment, the motor functions of the rats treated using i-ADSCs (LS+) did not differ greatly from those in the sham group and HE-stained brain tissue samples exhibited near-complete recovery with nearly no brain tissue damage. However, the motor functions of the rats treated using i-ADSCs (LS−) remained somewhat dysfunctional and tissue displayed necrotic scarring and voids. The western blot analysis also revealed significant expression of oligo-2 in the rats treated using i-ADSCs (LS+) as well as in the sham group (P < 0.05). The results demonstrated that low-level laser irradiation exerts a positive effect on the differentiation of i-ADSCs and can be employed to treat rats suffering from ischemic stroke to regain motor functions.
PMCID: PMC3865741  PMID: 24363769
2.  Low-Level Laser-Accelerated Peripheral Nerve Regeneration within a Reinforced Nerve Conduit across a Large Gap of the Transected Sciatic Nerve in Rats 
This study proposed a novel combination of neural regeneration techniques for the repair of damaged peripheral nerves. A biodegradable nerve conduit containing genipin-cross-linked gelatin was annexed using beta-tricalcium phosphate (TCP) ceramic particles (genipin-gelatin-TCP, GGT) to bridge the transection of a 15 mm sciatic nerve in rats. Two trigger points were irradiated transcutaneously using 660 nm of gallium-aluminum arsenide phosphide (GaAlAsP) via laser diodes for 2 min daily over 10 consecutive days. Walking track analysis showed a significant improvement in sciatic functional index (SFI) (P < 0.01) and pronounced improvement in the toe spreading ability of rats undergoing laser stimulation. Electrophysiological measurements (peak amplitude and area) illustrated by compound muscle action potential (CMAP) curves demonstrated that laser stimulation significantly improved nerve function and reduced muscular atrophy. Histomorphometric assessments revealed that laser stimulation accelerated nerve regeneration over a larger area of neural tissue, resulting in axons of greater diameter and myelin sheaths of greater thickness than that observed in rats treated with nerve conduits alone. Motor function, electrophysiological reactions, muscular reinnervation, and histomorphometric assessments all demonstrate that the proposed therapy accelerated the repair of transected peripheral nerves bridged using a GGT nerve conduit.
PMCID: PMC3662112  PMID: 23737818
3.  Mitochondrial protein ATPase family, AAA domain containing 3A correlates with radioresistance in glioblastoma 
Neuro-Oncology  2013;15(10):1342-1352.
ATPase-family, AAA domain containing 3A (ATAD3A) is located on human chromosome 1p36.33, and high endogenous expression may associate with radio- and chemosensitivity. This study was conducted to investigate the significance of ATAD3A in glioblastoma multiforme (GBM).
Clinical significance of ATAD3A expression was assessed by immunohistochemistry in 67 GBM specimens, and prognostic value was assessed in 32 GBM patients statistically. To investigate in vitro phenotypic effects of ATAD3A, cell viability was measured using a clonogenic survival assay under either knockdown or ectopic expression of ATAD3A in GBM cell lines. The effects of ATAD3A knockdown on targeted DNA repair-associated proteins in T98G cells were evaluated using immunofluorescence and Western blotting.
Clinically, high expression of ATAD3A was independent of O6-DNA methylguanine-methyltransferase methylation status and correlated with worse prognosis. In vitro, high ATAD3A-expressing T98G cells were more resistant to radiation-induced cell death compared with control and low endogenous ATAD3A U87MG cells. After silencing ATAD3A, T98G cells became more sensitive to radiation. On the other hand, enforced ATAD3A expression in U87MG cells exhibited increased radioresistance. ATAD3A may coordinate with aldo-keto reductase genes and participate in bioactivation or detoxication of temozolomide. Surprisingly, deficient DNA repair after irradiation was observed in T98G/ATAD3A knockdown as a result of decreased nuclear ataxia telangiectasia mutated kinase and histones H2AX and H3, which was also evidenced by the sustained elevation of poly (ADP-ribose) polymerase prior to and after radiation treatment.
Our data suggest that high expression of ATAD3A is an independent biomarker for radioresistance in GBM. ATAD3A could be a potential target for therapy.
PMCID: PMC3779036  PMID: 24057885
ATAD3A; autophagy; DNA repair; glioblastoma multiforme; radiation
4.  Celecoxib Suppresses the Phosphorylation of STAT3 Protein and Can Enhance the Radiosensitivity of Medulloblastoma-Derived Cancer Stem-Like Cells 
Medulloblastoma (MB) is a malignant primary brain tumor with poor prognosis. MB-derived CD133/Nestin double-positive cells (MB-DPs) exhibit cancer stem-like cell (CSC)-like properties that may contribute to chemoradioresistance, tumorigenesis and recurrence. In various tumors, signal transducer and activator of transcription 3 (STAT3) upregulation including MB which can regulate the expression of Nestin. Celecoxib, a selective COX-2 inhibitor, has been shown to potentially reduce STAT3 phosphorylation. The aim of the present study was to investigate the role of celecoxib in enhancing the effects of ionizing radiotherapy (IR) on MB-DP. MB-DPs and MB-derived CD133/Nestin double-negative cells (MB-DNs) were isolated from medulloblastoma cell line Daoy. Then, both of them were treated with celecoxib in different concentrations, and cell viability was assessed. The assays of cell survival, sphere formation, radiosensitivity, colony formation, apoptotic activity and mouse xenografting experiments in MB-DPs and MB-DNs treated with celecoxib alone, radiation alone, or celecoxib combined with radiation were further evaluated. We isolated MB-DPs from MB cell line Daoy, which exhibited typical CSC-like characteristics. Microarray analysis and Western blotting both indicated the upregulation of Janus kinase (JAK)-STAT cascade and STAT3 phosphorylation. Incubation with celecoxib dose-dependently suppressed the CSC-like properties and enhanced the IR effect on the induction of apoptosis, as detected by TUNEL assay and staining for Caspase 3 and Annexin V. Finally, celecoxib also enhanced the IR effect to suppress tumorigenesis and synergistically improve the recipient survival in orthotopic MB-derived CD133/Nestin double-positive cells (MB-DP cells) bearing mice.
PMCID: PMC4100195  PMID: 24945311
medulloblastoma; STAT3; celecoxib; CD133; Nestin; cancer stem-like cells
5.  Temporary clamping of bilateral external carotid arteries for surgical excision of a complex dural arteriovenous fistula 
Some complex dural arteriovenous fistulas (DAVFs) are lesions that typically have numerous arterial feeders. Surgery, including resection of fistulas or skeletonization of the diseased sinus, is still one of the important treatments for these lesions. However, major blood loss is usually encountered during craniotomy because of abundant arterial feeders from the scalp and transosseous vessels. We present a novel approach for obliteration of the fistulas with less blood loss.
Our first case was a 52-year-old male who suffered from syncope and seizure. Cerebral digital subtraction angiography (DSA) revealed complex DAVFs with numerous arterial feeders from bilateral external carotid arteries (ECAs) and drainage into the superior sagittal sinus with cerebral venous reflux. The second case was a 48-year-old male presenting with chronic headache. His DSA also showed complex DAVFs along the superior sagittal sinus with cerebral venous reflux. In both cases, we performed the surgical procedure to obliterate the pathological fistulas after temporary clamping of bilateral ECAs and noted less blood loss than in the conventional surgery.
The follow-up DSA showed successful obliteration of the complex DAVFs on the first case and partial improvement on the second case followed by transarterial embolization (TAE). The symptoms of the both patients were relieved after surgery with good recovery.
Temporary clamping of bilateral ECAs can improve the safety and ease the surgical excision for complex DAVFs. By using this technique, neurosurgeons can deal with aggressive DAVFs more confidently and calmly.
PMCID: PMC3927090  PMID: 24575325
Dural arteriovenous fistula; external carotid arteries; temporary clamping
6.  Luteolin inhibits migration of human glioblastoma U-87 MG and T98G cells through downregulation of Cdc42 expression and PI3K/AKT activity 
Molecular Biology Reports  2013;40(9):5315-5326.
Luteolin (3′,4′,5,7-tetrahydroxyflavone) is a common flavonoid in many types of plants and has several beneficial biological effects, including anti-inflammation, anti-oxidant, and anti-cancer properties. However, the detail mechanisms of luteolin in suppressing tumor invasion and metastasis are poorly understood. Here, we investigated the effects of luteolin on suppressing glioblastoma tumor cell invasion and migration activity. Under the non-cytotoxic doses (15 and 30 μM), luteolin exhibited an inhibitory effect on migration and invasion in U-87 MG and T98G glioblastoma cells. Additionally, filopodia assembly in U-87 MG cells was markedly suppressed after luteolin treatment. The treatment of luteolin also showed a decrease of Cdc42 (cell division cycle 42) protein levels and reduced PI3K/AKT activation, whereas there was no association between this decrease and phosphorylated ERK or altered transcription levels of Cdc42. Over expression of constitutive Cdc42 (Q61L) using transient transfection in U-87 MG cells induced a partial cell migration, but did not affected the degradation of the protein levels of Cdc42 after luteolin treatment. Moreover, inhibition of the proteaosome pathway by MG132 caused a significant recovery in the migration ability of U-87 MG cells and augmented the Cdc42 protein levels after luteolin treatment, suggesting that pharmacological inhibition of migration via luteolin treatment is likely to preferentially facilitate the protein degradation of Cdc42. Taken together, the study demonstrated that flavonoids of luteolin prevent the migration of glioblastoma cells by affecting PI3K/AKT activation, modulating the protein expression of Cdc42 and facilitating their degradation via the proteaosome pathway.
PMCID: PMC3751389  PMID: 23677714
Glioblastoma; Migration; Luteolin; PI3K/AKT; Cdc42; Proteasome degradation
7.  Endoscopic discectomy of L5-S1 disc herniation via an interlaminar approach: Prospective controlled study under local and general anesthesia 
Open discectomy remains the standard method for treatment of lumbar disc herniation, but can traumatize spinal structure and leaves symptomatic epidural scarring in more than 10% of cases. The usual transforaminal approach may be associated with difficulty reaching the epidural space due to anatomical peculiarities at the L5–S1 level. The endoscopic interlaminar approach can provide a direct pathway for decompression of disc herniation at the L5–S1 level. This study aimed to evaluate the clinical results of endoscopic interlaminar lumbar discectomy at the L5–S1 level and compare the technique feasibility, safety, and efficacy under local and general anesthesia (LA and GA, respectively).
One hundred twenty-three patients with L5–S1 disc herniation underwent endoscopic interlaminar lumbar discectomy from October 2006 to June 2009 by two spine surgeons using different anesthesia preferences in two medical centers. Visual analog scale (VAS) scores for back pain and leg pain and Oswestry Disability Index (ODI) sores were recorded preoperatively, and at 3, 6, and 12 months postoperatively. Results were compared to evaluate the technique feasibility, safety, and efficacy under LA and GA.
VAS scores for back pain and leg pain and ODI revealed statistically significant improvement when they were compared with preoperative values. Mean hospital stay was statistically shorter in the LA group. Complications included one case of dural tear with rootlet injury and three cases of recurrence within 1 month who subsequently required open surgery or endoscopic interlaminar lumbar discectomy. There were no medical or infectious complications in either group.
Disc herniation at the L5–S1 level can be adequately treated endoscopically with an interlaminar approach. GA and LA are both effective for this procedure. However, LA is better than GA in our opinion.
PMCID: PMC3130490  PMID: 21748045
General anesthesia; interlaminar approach; local anesthesia; lumbar disc herniation; percutaneous endoscopic discectomy
8.  Nasopharyngeal gangrenous abscess with skull base extension caused by Escherichia coli after esophageal dilatation for esophageal reconstruction 
Esophageal dilatation is the most widely used treatment option for the management of esophageal strictures. Complications include bleeding, brain abscess, esophageal perforation and bacteremia. Nasopharyngeal gangrenous abscess after the esophageal dilatation is very rare. Endonasal endoscopic surgery was performed to treat the lesion and a successful result was obtained.
Case Description:
A 59-year-old woman with a previous history of dilatation for esophageal stricture was admitted with a low-grade fever, headache, neck pain and cranial nerve abnormalities including sixth nerve palsy. Imaging studies aroused suspicion of necrotic retropharyngeal tumor with clivus, condylar process and cavernous sinus invasion. Biopsy with a pharyngosope was performed by an ENT doctor. The pathology showed acute necrotic inflammation, tissue granulation and bacteria colonies. Navigation with endonasal endoscopic surgery was chosen to treat the skull base and nasopharyngeal abscess. Bacterial culture showed Escherichia coli. Symptoms improved after the operation and treatment with antibiotics.
A nasopharyngeal gangrenous abscess with extension to the skull base in the case of esophageal reconstruction after esophageal dilatation is extremely rare. Physicians dealing with esophageal stricture should keep in mind that a nasopharyngeal abscess is a potential complication of esophageal dilatation.
PMCID: PMC2958327  PMID: 20975972
Endonasal endoscopic; esophageal dilatation; esophageal stricture; esophageal reconstruction; nasopharyngeal abscess; Escherichia coli
9.  Intradiscal electrothermal therapy in the treatment of chronic low back pain: Experience with 93 patients 
Low back pain (LBP) has become a main cause of absenteeism and disability in industrialized societies. Chronic LBP is an important health issue in modern countries. Discogenic LBP is one of the causes of chronic low back pain. The management of chronic discogenic LBP has been limited to either conservative treatment or operative treatment. Intradiscal electrothermal therapy (IDET) is now being performed as an alternative treatment.
Ninety-three consecutive patients undergoing IDET at 134 disc levels from October 2004 to January 2007 were prospectively evaluated. All patients had discogenic disease with chronic LBP, as determined by clinical features, physical examination and image studies, and had failed to improve with conservative treatment for at least 6 months. Follow-up period was from 1 week to 3 or more years postoperatively.
There were 50 male and 43 female patients, with a mean age of 46.07 years (range, 21-65 years). The results were classified as symptom free (100% improvement), better (≥50% improvement), slightly better (<50% improvement), unchanged and aggravated. Eighty-nine patients were followed up in the first week; of them, 77 (86.52%) patients had improvement (4, symptom free; 45, better; and 28, slightly better). The improvement rate gradually decreased to 80.90% in 1 year; and 73.91%, in 3 years.
In conclusion, IDET offers a safe, minimally invasive therapy option for carefully selected patients with chronic discogenic LBP who have not responded to conservative treatment. Although IDET appears to provide intermediate-term relief of pain, further studies with long-term follow-up are necessary.
PMCID: PMC2940097  PMID: 20847918
Chronic low back pain; intradiscal electrothermal therapy; discogenic pain
10.  Central neurocytoma: a clinical, radiological and pathological study of nine cases 
Clinical neurology and neurosurgery  2007;110(2):129-136.
Central neurocytoma is a rare intraventricular brain tumor that affects young adults and presents with increased intracranial pressure secondary to obstructive hydrocephalus. Typically, it has a favorable prognosis after adequate surgical intervention, but in some cases the clinical course is more aggressive. In this report, we describe the diagnosis and treatment of central neurocytoma in a series of patients at our institution.
Patients and Methods
Our series of nine patients (M:F=2:7, mean age, 28.2 years) with ventricular tumors showed typical radiological, histologic and immunohistochemical features of central neurocytoma. Most patients received craniotomy with removal of the tumor through transcallosal or transcortical approach. The surgical and histopathologic data of these patients were reviewed and analyzed.
The prognosis is generally favorable. Although most patients were alive and well at the last follow-up, two developed recurrence. Typical histologic features of recurrent neurocytoma include high proliferative activity (MIB-1 labeling index: 2.0–6.8%), prominent vascular proliferation and remarkable synaptophysin expression. Two patients (non-recurrent) died during follow-up due to sepsis or central failure. The MIB-1 labeling indices were as high as 2.2–5.4% for these two patients.
Although central neurocytoma is generally a benign neoplasm, some variant forms of recurrence are also present. Complete resection provides favorable long-term prognosis in most cases. Recurrent tumors are often local and the patients seem to recover well after a second resection followed by radiotherapy. Histologic features such as tumor proliferation (MIB-1 labeling index), vascular proliferation, and synaptophysin expression are often prominent in the recurrent tumor. We recommend that these histologic features be considered for tumor recurrence during treatment and follow-up of these patients.
PMCID: PMC2702989  PMID: 18022760
central neurocytoma; MIB-1 labeling index; proliferation; recurrence

Results 1-10 (10)