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Background: Tumor-associated NADH oxidase (tNOX; ENOX2) is a growth-related protein expressed in transformed cells. High concentrations of numerous chemotherapeutic agents have shown to inhibit tNOX activity and protein levels leading to a reduction in cell growth while little is known for the effects of low concentrations of chemotherapeutic agents on tNOX expression., Methods: Effects of chemotherapeutic agents on cell function were evaluated with traditional in vitro assays and the xCELLigence System. Western blot analyses were used to study protein expression profiles of the epithelial-to-mesenchymal transition., Results: We showed that doxorubicin treatment transiently up-regulates tNOX expression in human lung carcinoma A549 cells in association with enhanced cell migration. Similar results were observed in tamoxifen-exposed A549 cells. Furthermore, protein marker analyses revealed that the enhanced migration induced by tamoxifen was correlated with epithelial-to-mesenchymal transition, as evidenced by down-regulation of epithelial markers and up-regulation of mesenchymal markers. Importantly, tNOX overexpression enhanced cell migration, confirming the essential role of tNOX in cell migration., Conclusions: Based on these findings, we conclude that doxorubicin and tamoxifen induce a transient up-regulation of tNOX expression, leading to enhanced cell migration and EMT., General Significance: These findings establish an essential role for tNOX in cell migration and survival and may provide a rational framework for the further development of tNOX inhibitors as a novel class of antitumor agents., (Copyright © 2012 Elsevier B.V. All rights reserved.)

tNOX, a tumor-associated NADH oxidase, is a growth-related protein present in transformed cells. In this study, we employed RNA interference (RNAi)-mediated down-regulation of tNOX protein expression to explore the role of tNOX in regulating cell growth in human cervical adenocarcinoma (HeLa) cells. In this first reported use of RNAi to decrease tNOX expression, we found that HeLa cell growth was significantly inhibited by shRNA-knockdown of tNOX. Furthermore, cell migration and membrane association of Rac were decreased concomitantly with the reduction in tNOX protein expression. These results indicate that shRNA targeting of tNOX inhibits the growth of cervical cancer cells, and reduces cell migration via a decrease in the membrane association of Rac. We propose that tNOX is a potential upstream mediator of Rho activation that plays a role in regulating cell proliferation, migration, and invasion.

Tumor-associated NADH oxidase (tNOX, also known as ENOX2) is a growth-related protein expressed in transformed cells. Previous reports have revealed that the inhibition of tNOX activity by the anti-cancer drug, capsaicin, correlates with a reduction in growth of cancer cells, indicating a close relationship between tNOX activity and cell growth. Moreover, the study of depleted tNOX expression by RNA interference in HeLa cells suggests that it may be associated with the ability of tumor cells to acquire an aggressive phenotype, particularly in relation to cell proliferation. A key role for tNOX in regulating cell growth is further supported by the observation that the growth rate of MEF cells from tNOX-overexpressing transgenic mice is approximately two-fold greater than that of wild-type cells. The purpose of this study was to investigate the anti-proliferative effect of capsaicin on tNOX expression level in stomach cancer cells. We showed that capsaicin induced cytotoxicity in SCM cells concomitantly with apoptosis, PARP cleavage, and down-regulation of tNOX protein.

Treatment for chronic atlanto-axial instability remains problematic despite recent innovations in new surgical techniques and instrumentation. Our team reviewed a series of 23 cases of patients with chronic atlanto-axial instability who underwent posterior transarticular screw fixation operations between May 1998 and September 2002. Etiologies of these patients included failed prior surgery, rheumatoid arthritis, congenital anomalies and old odontoid fractures. The clinical presentations were nuchal pain and cervical myelopathy or radiculopathy, with sensory and/or motor deficits that persisted for more than 3 months. We routinely used external reduction to realign the C1-C2 axis prior to operating, and operated on patients using halo-vest fixation. After surgery, the halo-vest was replaced by a collar. In the post-operative follow-up, 22 of the 23 patients (96%) were found to have achieved solid, bony or fibrous union of the C1-C2 axis. Eleven of the 14 (79%) patients with pre-operative neck pain experienced immediate relief or significant improvement. Thirteen of the 20 patients (65%) with myelo-radiculopathy demonstrated improvement of previous motor deficits. Major morbidity included a vertebral artery (VA) injury and a malpositioned screw. No cases of mortality or neurological complications occurred in this series. Posterior transarticular C1-C2 screw fixation results in a high fusion rate without the additional need for rigid external immobilization. It allows good neurological recovery in cases of chronic atlanto-axial instability. Judicious pre-surgical planning and meticulous operative technique may avoid neurological complications and vertebral artery injury.

Background: Fat within the cerebral falx is commonly encountered in our daily practice but has never been characterized and reported. The purpose of this study was to determine the incidence of fat within the cerebral falx and to identify its clinical features., Methods: The cerebral falx was prospectively imaged in 1,570 consecutive brain computed tomographic scans and its features characterized. Cerebral magnetic resonance imaging was done in some patients., Results: Of the 1,570 cases studied, 115 revealed a small amount of fat in the cerebral falx. This fat had a purely negative Hounsfield value. It produced a high signal on both T1- and T2-weighted magnetic resonance images. There was no calcified component. The fat was seen most commonly in aged patients. No related symptoms were noted., Conclusions: Among the patients studied, fat in the cerebral falx had an incidence of 7.3%. It is an incidental finding in adults and requires no further evaluation or treatment.

Aberrant cervical carotid artery is an uncommon anomaly. Because this anomaly can lie in close proximity to the midline of the posterior part of the pharynx, it poses a significant risk during both major pharyngeal tumor resection and less extensive procedures such as tonsillectomy, adenoidectomy and palatopharyngoplasty. Five cases of aberrant cervical carotid artery were encountered and diagnosed using computerized tomography. In all five cases, the anomalous finding did not correlate with the presenting symptoms. Computerized tomographic images of these cases are provided. A review of the literature and the embryology of the aberrant carotid artery are presented. Awareness of the anomaly by radiologists and surgeons is essential to avoid accidental injury to the vessel during surgery.

Gas within the cavernous sinus is an unusual finding. We report three patients who demonstrated gas in the cavernous sinus on computerized tomography (CT). The clinical information of these patients was reviewed for the possible source of the gas and the symptoms induced by the gas. Cavernous sinus gas was seen in two patients with sphenoid sinus fracture and in one patient after intravenous fluid infusion. None of the patients had symptoms referable to the cavernous sinus gas, but one patient had a grave prognosis due to trauma. Identification of cavernous sinus gas on CT and correlation with the clinical information is mandatory for further management.

Background: Far lateral lumbar disc herniation is an uncommon condition that may compress the nerve root outside the vertebral canal and in its extraforaminal course. The traditional midline interlaminar approach for the exploration of far lateral lumbar disc herniation is often difficult because the intervertebral articulation obviates a direct view of the course of the extraspinal nerve. In this report, we present two surgical approaches for the treatment of far lateral lumbar disc herniation: the paramedian muscle-splitting microtechnique and the enlarged midline approach., Methods: Eight patients with far lateral lumbar disc herniation were found among 160 lumbar disc operations in 160 patients. According to computed tomography results, we divided patients with far lateral lumbar disc herniations into two groups; the extraforaminal and foraminal groups. Clinical presentation, imaging studies and surgical approach were thoroughly reviewed., Results: Three patients in the extraforaminal group underwent the paramedian muscle-splitting microtechnique. Two patients in the foraminal group underwent the enlarged midline approach. The other three were operated on before the introduction of the paramedian muscle-splitting microtechnique and the enlarged midline approach. One of these patients who underwent the traditional interlaminar approach with resection of the lateral portion of facet joint, received additional instrumentation and fusion for the prevention of further instability. All had good results and no further surgical treatment was necessary., Conclusions: The incidence of far lateral lumbar disc herniation was 5% of all surgically treated disc herniations at our institution. For the extraforaminal group, the paramedian muscle-splitting microtechnique is the surgical route of choice. For the foraminal group, the enlarged midline approach is better than the traditional, interlaminar approach in saving the facet joint and preventing postoperative instability.

Background: Ultrasound scanning is a well-established means of evaluating intracranial structures in infants and children with open fontanelles. However, it remains underutilized in neurosurgical operations. We present our experience with the intraoperative use of realtime ultrasonography during 36 neurosurgical procedures., Methods: Thirty-six intraoperative ultrasonography (IOUS) procedures were performed over the past two years. Thirty-two patients had intracranial lesions and four had intraspinal tumors. A real-time scanner equipped with a 5 MHz and a 7.5 MHz transducer was used during surgery., Results: IOUS worked well, regardless of the location of the craniotomy site. It was useful in localizing and characterizing intracranial and intraspinal masses, assuring the completeness of tumor removal (22 cases), proper positioning of ventricular shunt catheters (5 cases), guiding and confirming the decompression of cysts or abscesses (3 cases) and real time monitoring of surgical complications (36 cases)., Conclusions: IOUS can be helpful in defining intracranial and intraspinal lesions as well as normal architecture. It shortens the operative time and decreases the surgical morbidity. The expertise of the physician with sonographic equipment facilitates its accurate and expedient intraoperative neurosurgical application.

Olivary hypertrophy (OH) is not a primary lesion but, rather, develops as a lesion of the Guillain-Morraret triangle, which is composed of the contralateral dentate nucleus, the ipsilateral red nucleus and the ipsilateral inferior olivary nucleus. OH is usually accompanied by palatal myoclonus or other involuntary movements such as extremity myorhythmia. One case of unilateral OH following ipsilateral pontine tegmental hemorrhage is presented. Magnetic resonance imaging (MRI) showed high signal intensity in the inferior olivary nuclei on T2- and proton-density-weighted images. Enlargement of the inferior olivary nuclei was also noted. MRI may currently be the only procedure capable of confirming the diagnosis.

Background: High-resolution, real time, intraoperative ultrasonography (IOUS) has been used in a number of cases in our neurosurgical department to identify, localize and characterize intracranial abnormalities. We compare the images of IOUS with those of computerized tomography (CT) and magnetic resonance imaging (MRI) in order to enhance our experience and confidence., Methods: IOUS images were compared with preoperative CT scans and/or MRIs in 30 intracranial masses. Tumor size and margin, echogenicity and edema were the features compared., Results: The images of IOUS, CT and MRI correlated closely except for images of primary gliomas. IOUS was more effective than CT and MRI in delineating the extent of a glioma, determining whether a lesion was cystic, with or without septation, or solid and in guiding surgical procedures. The contrast enhancement available with CT and MRI could not be demonstrated with IOUS., Conclusions: IOUS provides exquisite detail of intracranial pathology as well as, or even better than, CT and MRI. Its application should be emphasized to minimize damage of normal brain tissue and increase the completeness of tumor resection.

A 71-year-old woman had arachnoid granulations found in the straight and transverse sinuses on computerized tomography (CT) and magnetic resonance imaging (MRI). The arachnoid granulations appeared as low-density masses on CT. They gave low signals on T1-weighted MR images and high signals on T2-weighted images. Arachnoid granulations are usually of no clinical significance. They have characteristic CT and MRI manifestations and should not be mistaken for sinus thrombosis or intrasinus tumors.

Lateral thoracic meningoceles are rare and, in most cases, they are associated with neurofibromatosis. We report a case in which computerized tomography (CT)-myelography established the diagnosis of multiple, bilateral, lateral, thoracic meningoceles without neurofibromatosis. Plain film radiographs are necessary to evaluate any associated kyphoscoliosis and its progression. CT and magnetic resonance imaging demonstrate the extent of bony erosion, and the size and number of lateral thoracic meningoceles. CT-myelography reveals contrast medium in the meningoceles and is the major diagnostic imaging modality.

Background: High resolution computed tomography (HRCT) is highly efficient in demonstrating the anatomy of the temporal bone. This study evaluates its application to temporal bone fractures (TBF)., Methods: We collected data from 26 cases of TBF in the past two years. All cases underwent HRCT examination. The clinical information was reviewed and correlated with the imaging findings., Results: Eighty-six percent of the cases had longitudinal fractures. Axial scans were the most useful in identifying the fracture line. Mastoid opacification on routine head computed tomography (CT) was also useful in indicating possible TBFs. Complications of TBF, such as ossicular chain disruption, facial nerve damage or otorhino-liquorrhea, were identified clearly using HRCT., Conclusions: To minimize or prevent the sequelae of TBF, accurate radiologic evaluation is necessary as soon as possible after injury. HRCT of the temporal bone delineates the bony and soft tissue anatomy with high accuracy and we recommend it as the diagnostic modality of choice.

Background: Surgery of the anterior skull base confronts with the life-threatening risks of infection and cerebrospinal fluid (CSF) leakage, especially after extensive tumor resection. Avoidance of these complications demands a good intraoperative reconstruction. The technical feasibility has been demonstrated in previous reports. A judicious rationale of surgical principle is investigated in review of our patients and other series., Methods: Fourteen cases underwent neurosurgical procedures involving the anterior skull base by the authors between June 1992 and January 1994. Five patients with trauma, 1 with inflammation, and 8 with space-occupying lesion were included. The modality of skull base reconstruction and patients' outcome were evaluated., Results: Eleven of these cases accepted reconstructive procedures to some extent including pericranium, lyodura, tissue glue, bone graft and muscle flaps. Four cases of traumatic CSF leakage were successfully repaired after anterior skull base reconstruction. One case with traumatic optic neuropathy restored vision after surgical optic nerve decompression. A rhinogenic infected discharging sinus was cured with pedicle island flap obliteration. Space-occupying lesions in 8 cases were totally removed without postoperative wound infection, CSF leakage, or meningitis, of which 2 cases of malignancy recurred 7 and 5 months after operation respectively. The follow-up period was from 5 to 26 months with a mean of 14 months., Conclusions: Meticulous reconstruction with different possibilities of closure is the cornerstone of anterior skull base surgery, in spite of its difficulties and needs for extensive resection. Combined craniofacial resection could achieve "en bloc" or radical excision of "inoperable" anterior skull base lesions confidently with low morbidity and mortality based on skillful reconstructive techniques.

Of 200 patients with acoustic neurinoma undergoing an operation via the retrosigmoid transmeatal approach in the semisitting position, 18 patients had a high jugular bulb on the tumor side. The frequency was 9%. From a neurosurgical point of view, a jugular fossa above the low border of the internal auditory canal (IAC) is classified as a high one. All 200 patients were evaluated by computed tomography with bone window reconstruction of high-resolution thin axial slices (1.5 mm). High jugular bulbs were classified into three grades as follows: Grade I, jugular bulb situated less than 1.5 mm above the low border of IAC; Grade II, jugular bulb between 1.5 and 3.0 mm above the low border of the IAC; Grade III, jugular bulb > 3 mm above the low border of IAC. There were eight patients with Grade I, six patients with Grade II, and four patients with Grade III. In these patients, in order to open the IAC without concomitant injury of the jugular bulb, the superior posterior portion of the porus was drilled away. Opening the jugular fossa was unavoidable in Grade III cases. No difference was noted in functional preservation of facial or cochlear nerve between HJB cases and normal jugular bulb cases, but HJB cases had a higher frequency of air embolism during tumor removal than did normal cases (16 versus 5%), especially Grade III cases (two of four). There was no mortality or morbidity in the cases of air embolism. Details of the surgical procedure in such cases are discussed.