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Find video protocols related to scientific articles indexed in Pubmed.
Discovery and Characterization of the Tuberculosis Drug Lead Ecumicin.
Org. Lett.
PUBLISHED: 11-20-2014
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The new tuberculosis (TB) lead ecumicin (1), a cyclic tridecapeptide, was isolated from Nonomuraea sp. MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS(2). Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey's analysis.
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Childhood Trauma, Parental Death, and Their Co-occurrence in Relation to Current Suicidality Risk in Adults: A Nationwide Community Sample of Korea.
J. Nerv. Ment. Dis.
PUBLISHED: 11-06-2014
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Background: Although previous studies have suggested that childhood trauma and parental death are strongly associated with suicidality in adulthood, it is still unclear how these factors interact within the same population. A total of 1396 adults were recruited through nationwide multistage probability sampling in South Korea. Subjects were evaluated through face-to-face interviews using the Suicidality Module of the Mini-International Neuropsychiatric Interview and the Early Trauma Inventory Self Report-Short Form. Among the 1396 adults, the group that experienced both childhood trauma and parental death had the highest current suicidality risks (F = 12.16, p < 0.0001) and lifetime suicide attempt (? = 35.81, p < 0.0001) compared with the other groups, which were only childhood trauma, only parental death, and neither. Multivariate logistic regression analyses revealed that middle-to-high current suicidality risk and lifetime suicide attempt were significantly associated with concurrent childhood trauma and parental death (odds ratio, 3.64; 95% confidence interval, 1.99-6.65) as well as with only childhood trauma (odds ratio, 1.95; 95% confidence interval, 1.33-2.87), after adjusting for age, sex, education, marital status, household monthly income, and living area. Emotional abuse was the only type of childhood trauma significantly associated with higher current suicidality scores in those who experienced childhood parental death than in those who did not (F = 3.26, p = 0.041). Current suicidality risk and lifetime suicide attempt are associated with experiencing both parental death and trauma, especially emotional abuse, in childhood, whereas experiencing only childhood parental death is associated with neither.
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TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis.
Sci Transl Med
PUBLISHED: 10-24-2014
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TOPK (T-lymphokine-activated killer cell-originated protein kinase) is highly and frequently transactivated in various cancer tissues, including lung and triple-negative breast cancers, and plays an indispensable role in the mitosis of cancer cells. We report the development of a potent TOPK inhibitor, OTS964 {(R)-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one}, which inhibits TOPK kinase activity with high affinity and selectivity. Similar to the knockdown effect of TOPK small interfering RNAs (siRNAs), this inhibitor causes a cytokinesis defect and the subsequent apoptosis of cancer cells in vitro as well as in xenograft models of human lung cancer. Although administration of the free compound induced hematopoietic adverse reactions (leukocytopenia associated with thrombocytosis), the drug delivered in a liposomal formulation effectively caused complete regression of transplanted tumors without showing any adverse reactions in mice. Our results suggest that the inhibition of TOPK activity may be a viable therapeutic option for the treatment of various human cancers.
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RRAD Promotes EGFR-Mediated STAT3 Activation and Induces Temozolomide Resistance of Malignant Glioblastoma.
Mol. Cancer Ther.
PUBLISHED: 10-13-2014
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Glioblastoma multiforme (GBM) is an extremely aggressive brain cancer with a median survival of less than two years. GBM is characterized by abnormal activation of receptor tyrosine kinase and constitutively activated STAT3. Although EGFR phosphorylation and STAT3 activation are essential for the maintenance of GBM cancer stem cells, the molecular mechanism underlying endosome-mediated STAT3 activation is not fully understood at present. In the current study, we showed that GTP-binding protein RRAD (RAS associated with diabetes, RAD) physically associates with EGFR, and EEA1, enhancing the stability and endosome-associated nuclear translocation of EGFR. Functionally, RRAD contributes to the activation of STAT3 and expression of the stem cell factors, OCT4, NANOG, and SOX2, thereby enhancing self-renewing ability, tumor sphere formation, EMT, and in vivo tumorigenesis. Most importantly, RRAD contributes to poor survival in GBM patients. RRAD expression is correlated with temozolomide resistance, and conversely, depletion of RRAD leads to sensitization of highly temozolomide-resistant GBM cells. Our data collectively support a novel function of RRAD in STAT3 activation, and provide evidence that RRAD acts as a positive regulator in the EGFR signaling pathway. These results demonstrate a critical role for RRAD in GBM tumorigenesis, and provide a rationale for the development of pharmacological inhibitors of RRAD in GBM.
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Designing an ultrathin silica layer for highly durable carbon nanofibers as the carbon support in polymer electrolyte fuel cells.
Nanoscale
PUBLISHED: 09-08-2014
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A critical issue for maintaining long-term applications of polymer electrolyte fuel cells (PEFCs) is the development of an innovative technique for the functionalization of a carbon support that preserves their exceptional electrical conductivity and robustly enriches their durability. Here, we report for the first time how the formation of a partially coated, ultrathin, hydrophobic silica layer around the surfaces of the carbon nanofiber (CNF) helps improve the durability of the CNF without decreasing the significant electrical conductivity of the virgin CNF. The synthesis involved the adsorption of polycarbomethylsilane (PS) on the CNF's sidewalls, followed by high temperature pyrolysis of PS, resulting in a highly durable, conductive carbon support in PEFCs. The Pt nanoparticles are in direct contact with the surface of the carbon in the empty spaces between unevenly coated silica layers, which are not deposited directly onto the silica layer. The presence of a Pt nanoparticle layer that was thicker than the silica layer would be a quite advantageous circumstance that provides contact with other neighboring CNFs without having a significant adverse effect that deeply damages the electrical conductivity of the neighboring CNF composites with the silica layer. Furthermore, the ultrathin, hydrophobic silica layer around the surfaces of the CNF provides great potential to reduce the presence of water molecules in the vicinity of the carbon supports and the ?OH radicals formed on the surface of the Pt catalyst. As a result, the CNF with a 5 wt% silica layer that we prepared has had extremely high initial performance and durability under severe carbon corrosion conditions, starting up with 974 mA cm(-2) at 0.6 V and ending up with more than 58% of the initial performance (i.e., 569 mA cm(-2) at 0.6 V) after a 1.6 V holding test for 6 h. The beginning-of-life and end-of-life performances based on the virgin CNF without the silica layer were 981 and 340 mA cm(-2) at 0.6 V, respectively. The CNF having a silica layer had long-term durability which was superior to that of the virgin CNF.
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Gamma Knife radiosurgery for meningiomas arising from the tentorium: a 22-year experience.
J. Neurooncol.
PUBLISHED: 09-04-2014
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In order to evaluate long term clinical and imaging outcomes, the authors retrospectively reviewed our 22-year experience using stereotactic radiosurgery (SRS) for tentorial meningiomas. Thirty-nine patients with tentorial meningiomas underwent SRS using various Gamma Knife technologies between 1988 and 2010. The most common presenting symptoms were headache, dizziness or disequilibrium, and ataxia. The median tumor volume was 4.6 cm(3) (range 0.5-36.6 cm(3)) and the median radiation dose to the tumor margin was 14 Gy (range 8.9-18 Gy). The median follow-up period was 41 months (range 6-183 months). At the last imaging follow-up, tumor volumes decreased in 22 patients (57 %), remained stable in 13 patients (33 %), and increased in 4 patients (10 %). The progression-free survival after SRS was 97 % at 1 year, and 92 % at 5 years. At the last clinical follow-up, 35 patients (90 %) showed no change in symptoms, 1 patient (2 %) showed improvement of their neurologic symptom, and 3 patients (8 %) demonstrated worsening symptoms. The rate of symptom worsening after SRS was 5 % at 1 year, and 10 % at 5 years. Asymptomatic peritumoral edema after SRS occurred in 2 patients (5 %). Symptomatic adverse radiation effect developed in 2 patients (5 %). SRS for tentorial meningiomas provided long-term effective tumor control and a low risk of radiation related complications.
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A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine.
Eur. J. Hum. Genet.
PUBLISHED: 08-20-2014
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Hereditary sensorineural hearing loss is an extremely clinical and genetic heterogeneous disorder in humans. Especially, syndromic hearing loss is subdivided by combinations of various phenotypes, and each subtype is related to different genes. We present a new form of progressive hearing loss with migraine found to be associated with a variant in the ATP1A2 gene. The ATP1A2 gene has been reported as the major genetic cause of familial migraine by several previous studies. A Korean family presenting progressive hearing loss with migraine was ascertained. The affected members did not show any aura or other neurologic symptoms during migraine attacks, indicating on a novel phenotype of syndromic hearing loss. To identify the causative gene, linkage analysis and whole-exome sequencing were performed. A novel missense variant, c.571G>A (p.(Val191Met)), was identified in the ATP1A2 gene that showed co-segregation with the phenotype in the family. In silico studies suggest that this variant causes a change in hydrophobic interactions and thereby slightly destabilize the A-domain of Na(+)/K(+)-ATPase. However, functional studies failed to show any effect of the p.(Val191Met) substitution on the catalytic rate of this enzyme. We describe a new phenotype of progressive hearing loss with migraine associated with a variant in the ATP1A2 gene. This study suggests that a variant in Na(+)/K(+)-ATPase can be involved in both migraine and hearing loss.European Journal of Human Genetics advance online publication, 20 August 2014; doi:10.1038/ejhg.2014.154.
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Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.
Lancet Oncol.
PUBLISHED: 08-19-2014
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Cilengitide is a selective ?v?3 and ?v?5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter.
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Determination of EC95 of Remifentanil for Smooth Emergence From Propofol Anesthesia in Patients Undergoing Transsphenoidal Surgery.
J Neurosurg Anesthesiol
PUBLISHED: 08-07-2014
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In patients undergoing pituitary surgery using a transsphenoidal approach, anesthesia emergence should be smooth with minimal coughing. Recent studies demonstrated that a target-controlled infusion of remifentanil effectively suppresses coughing induced by the endotracheal tube. We investigated the EC95 of remifentanil for smooth emergence without coughing from propofol anesthesia in patients undergoing transsphenoidal hypophysectomy.
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Evaluation of risk factors for vertebral compression fracture after stereotactic radiosurgery in spinal tumor patients.
Korean J Spine
PUBLISHED: 08-04-2014
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Stereotactic radiosurgery (SRS) is an emerging treatment modality for malignant spinal tumors. After SRS, some patients suffered from pain aggravation due to development of vertebral compression fracture (VCF). In these cases, surgery should be considered.
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Hemorrhagic Recurrence in Diffuse Astrocytoma without Malignant Transformation.
Brain Tumor Res Treat
PUBLISHED: 07-31-2014
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Although uncommon, hemorrhage can be a complication of low grade glioma with an unfavorable prognosis such as transformation to higher grade glioma. To our knowledge, hemorrhagic recurrence of World Health Organization Grade II, diffuse astrocytoma without malignant transformation has not been reported. Thus, we report a case of diffuse astrocytoma with hemorrhagic recurrence without malignant transformation. The patient had undergone craniotomy and tumor removal 7 years previously. Annual follow-up MRIs had shown evidence of slow tumor recurrence. With the sudden onset of seizure, the patient was diagnosed as hemorrhagic recurrence and underwent second tumor removal highly suspecting malignant change into higher grade glioma. Histopathology confirmed diffuse astrocytoma without malignant changes. As the patient's postoperative condition was excellent, we plan to withhold chemotherapy and radiation therapy for use as a later treatment option.
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Extracapsular en bloc resection in pituitary adenoma surgery.
Pituitary
PUBLISHED: 07-28-2014
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A pituitary pseudocapsule often contains tumor tissue and should be removed for radical resection. It can be used as a surgical plane for more radical resection of the tumor in many cases of pituitary adenomas. We evaluated the advantages and disadvantages of extracapsular en bloc capsulectomy.
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Clinical use of diffusion tensor image-merged functional neuronavigation for brain tumor surgeries: review of preoperative, intraoperative, and postoperative data for 123 cases.
Yonsei Med. J.
PUBLISHED: 07-23-2014
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To achieve maximal safe resection during brain tumor surgery, functional image-merged neuronavigation is widely used. We retrospectively reviewed our cases in which diffusion tensor image (DTI)-merged functional neuronavigation was performed during surgery.
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Isolated Central Nervous System Relapse of Acute Lymphoblastic Leukemia.
Brain Tumor Res Treat
PUBLISHED: 07-21-2014
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Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and may exhibit central nervous system (CNS) involvement. Advances in chemotherapy and effective CNS prophylaxis have significantly decreased the incidence of CNS relapse of ALL to 5-10%. Here, we report the case of a patient with isolated CNS relapse of standard risk group pre-B-cell type ALL in an 11-year-old girl, relapsed 3 years after successful completion of chemotherapy. An 11-year-old girl visited our hospital complaining of headache, dizziness, vomiting, and visual field defects. Neurological examination revealed left-side homonymous hemianopsia. Brain magnetic resonance imaging showed a large irregular dural-based sulcal hematoma in the right parietal and occipital lobes. Surgery to remove the hematoma revealed the existence of hematopoietic malignancy after pathologic evaluation. Bone marrow biopsy was subsequently performed but showed no evidence of malignancy.
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Adult-Onset Sellar and Suprasellar Atypical Teratoid Rhabdoid Tumor Treated with a Multimodal Approach: A Case Report.
Brain Tumor Res Treat
PUBLISHED: 07-15-2014
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We report a very rare case of sellar and suprasellar atypical teratoid rhabdoid tumor (ATRT) in a 42-year-old female patient. The tumor was removed subtotally with a transsphenoidal approach. Histopathologic study showed rhabdoid cells with prominent nucleoli and abundant cytoplasm. Immunohistochemistry for INI1 was completely negative in the tumor cells, consistent with ATRT. After surgery, she received radiotherapy including spinal irradiation with proton beam therapy and subsequent chemotherapy, with no evidence of recurrence for more than 2 years. Up to date, this is the 8th case of an adult-onset ATRT in the sellar or suprasellar region. Despite its rarity, ATRTs should be considered in the differential diagnosis of an unclear malignant sellar or suprasellar lesion in adult patients and the treatment strategies for adult ATRT patients could be differentiated from those of pediatric ATRT patients.
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Changes in graft thickness after skull defect reconstruction with autogenous split calvarial bone graft.
J Craniofac Surg
PUBLISHED: 07-10-2014
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The ideal material for primary reconstruction of skull defect would be the autogenous bone. However, the long-term evaluation regarding the change in bone graft thickness has not been reported. In this article, we analyzed the thickness changes of the graft according to the time period. Between March 2005 and February 2011, a total of 29 patients underwent skull reconstruction with autogenous split calvarial bone grafts. After applying exclusion criteria, computed tomographic (CT) images of 15 patients were analyzed. The donor bone was harvested in full thickness as 1 piece and then as split. One half of the bone plate was transferred to the defect site; the other half, to the donor site. Both halves were fixed with titanium plates. To compare graft thickness changes, immediate postoperative and follow-up CT scans were analyzed by a single researcher. An anatomic reference was appointed for each patient, and the thickness of the graft on the same level was measured on time-series CT images. Collected data were analyzed with a polynomial random coefficient model. The main causes of the skull defects were trauma and tumor excision. In all cases, the graft thickness was not decreased but even increased in both the donor and recipient sites. The mean graft thicknesses between 6 months and 1 year after the surgery as well as those between 2 and 3 years after the surgery were 1.24-times and 1.56-times thicker than the immediate postoperative thickness, respectively. Graft thickness turned out to be either maintained or increased over time.
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Procarbazine, CCNU, and Vincristine Chemotherapy in Gliomatosis Cerebri.
Brain Tumor Res Treat
PUBLISHED: 07-02-2014
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A 49-year-old female patient was admitted due to memory disturbances. Magnetic resonance (MR) imaging suggested gliomatosis cerebri (GC), which had spread to both insular lobes, both frontal and basal ganglia and the brain stem. A stereotactic biopsy was performed at the high signal intensity area of the T2-weighted MR image, and the revealed a diffuse astrocytoma. Radiation therapy was judged not to be an appropriate treatment for the patient because of her cognitive impairment. A combinatorial chemotherapy regiment consisting of Procarbazine, CCNU, and Vincristine (PCV) was agreed upon after discussion. The patient underwent six cycles of PCV chemotherapy (a full dose was applied until the 3rd cycle, and dose then was reduced to 75% for the remaining cycles). Although the patient exhibited side effects such as bone marrow suppression and gastrointestinal symptoms, these were managed by medication. Over the 28 months following initiation of treatment, the high signal area in the right frontal and temporal lobes in the T2-weighted MR image decreased, and the patient's cognitive function [global deterioration scale (GDS) 4 points, mini-mental state examination (MMSE) 25 point] also improved (GDS 1 points, MMSE 29 points). PCV chemotherapy can therefore be an alternative therapeutic option for patients with GC who cannot be treated with radiation therapy or other chemotherapies.
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Clinical predictors of GH deficiency in surgically cured acromegalic patients.
Eur. J. Endocrinol.
PUBLISHED: 06-27-2014
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Even in patients with cured acromegaly, GH deficiency (GHD) after transsphenoidal adenomectomy (TSA) adversely affects body composition and inflammatory biomarkers of cardiovascular risk. In this study, clinical parameters for predicting GHD after TSA in 123 cured acromegalic patients were investigated.
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KML001, a telomere-targeting drug, sensitizes glioblastoma cells to temozolomide chemotherapy and radiotherapy through DNA damage and apoptosis.
Biomed Res Int
PUBLISHED: 06-26-2014
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Standard treatment for glioblastoma comprises surgical resection, chemotherapy with temozolomide, and radiotherapy. Nevertheless, majority of glioblastoma patients have recurrence from resistance to the cytotoxic conventional therapies. We examined combinational effects of KML001, an arsenic compound targeting telomeres of chromosomes with temozolomide or irradiation, in glioblastoma cell lines and xenograft models, to overcome the therapeutic limitation of chemoradiation therapy for glioblastoma. Although KML001 alone showed little effects on in vitro survival of glioblastoma cells, cell death by in vitro temozolomide treatment or irradiation was synergistically potentiated by combination with KML001. Since phosphorylated ?-H2AX, cleaved casepase-3, and cleaved PARP were dramatically increased by KML001, the synergistic effects would be mediated by increased DNA damage and subsequent tumor cell apoptosis. Combinatorial effects of KML001 were observed not only in chemo- and radiosensitive glioblastoma cell line, U87MG, but also in the resistant cell line, U251MG. In the U87MG glioblastoma xenograft models, KML001 did not have systemic toxicity but showed synergistic therapeutic effects in combination with temozolomide or irradiation to reduce tumor volumes significantly. These data indicated that KML001 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for glioblastoma.
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Prediction of methylguanine methyltransferase promoter methylation in glioblastoma using dynamic contrast-enhanced magnetic resonance and diffusion tensor imaging.
J. Neurosurg.
PUBLISHED: 06-20-2014
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The methylation status of the methylguanine methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma. The authors aimed to assess whether MGMT methylation status can be predicted by dynamic contrast-enhanced (DCE) MRI and diffusion tensor imaging (DTI).
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Disseminated Hemangioblastoma of the Central Nervous System without Von Hippel-Lindau Disease.
Brain Tumor Res Treat
PUBLISHED: 06-19-2014
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Hemangioblastoma (HB) of the central nervous system may occur sporadically or in association with von Hippel-Lindau (VHL) disease. Disseminated HB means malignant spread of the original primary HB without local recurrence at surgically resected site. It has been rarely reported previously, and rarer especially without VHL gene mutation. We report a case of disseminated HB without VHL disease. A 59-year-old man underwent a surgery for total removal of a cerebellar HB. From five years after the surgery, multiple dissemination of HB was identified intracranially and he subsequently underwent cyberknife radiosurgery. The lesions got smaller temporarily, but they soon grew larger. Nine years after the initial surgery for cerebellar HB, he showed severe back pain. His magnetic resonance image of spine revealed intradural extramedullary mass at T6-7 level. Complete surgical removal of the mass was performed and the pathological diagnosis was identical to the previous one. He had no evidence of VHL disease. And there was no recurrence of the tumor at the site of the original operation. The exact mechanism of dissemination is unknown, but the surgeon should be cautious of tumor cell spillage during surgery and prudently consider the decision to perform ventriculo-peritoneal shunt. In addition, continuous follow-up for recurrence or dissemination is necessary for patients even who underwent complete removal of cerebellar HB.
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Immunoglobulin G4-Related Hypertrophic Pachymeningitis with Skull Involvement.
Brain Tumor Res Treat
PUBLISHED: 06-12-2014
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Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, defined as focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease. Moreover, cases involving bone are even rarer. In this report, the authors describe a case of IgG4-related hypertrophic pachymeningitis involving the skull in a 65-year-old man presenting with generalized tonic seizures. There is a 2.4 cm diameter extra-axial mass at the vertex of the left frontal convexity and thickened dura mater with contrast enhancement on magnetic resonance (MR) imaging. In addition, the skull adjacent to the mass was focally enhanced. He underwent surgical resection of the enhanced mass and skull. Histopathological findings revealed chronic inflammation with fibrosis, and idiopathic hypertrophic intracranial pachymeningitis was considered. However, eight months after surgery, partial seizures developed and brain MR imaging revealed a recurrence adjacent to the previous mass. We decided to perform additional immunohistochemical staining of the previous specimen, instead of a re-excision. Immunohistochemical staining showed markedly increased IgG4 (+) plasma cells. Consequently, IgG4-related hypertrophic meningitis was confirmed. Since then, steroids and immunosuppressant medications were started. Follow-up MR imaging at 3 months after medication initiation demonstrated complete remission. In conclusion, IgG4-related hypertrophic pachymeningitis should be considered in the differential diagnosis of hypertrophic cranial pachymeningitis.
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Fractionated Gamma Knife Radiosurgery for Benign Perioptic Tumors: Outcomes of 38 Patients in a Single Institute.
Brain Tumor Res Treat
PUBLISHED: 06-10-2014
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This study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions.
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Treatment and Outcomes for Gangliogliomas: A Single-Center Review of 16 Patients.
Brain Tumor Res Treat
PUBLISHED: 05-29-2014
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Ganglioglioma is a rare and slowly growing benign tumor. We investigated the outcomes of patients who underwent different combination treatments.
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Preliminary study of neurocognitive dysfunction in adult moyamoya disease and improvement after superficial temporal artery-middle cerebral artery bypass.
J Korean Neurosurg Soc
PUBLISHED: 05-13-2014
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Moyamoya disease (MMD) is a chronic cerebrovascular occlusive disease of unknown etiology. In addition, the neurocognitive impairment of adults with MMD is infrequently reported and, to date, has not been well described. We attempted to determine both the neurocognitive profile of adult moyamoya disease and whether a superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis can improve the neurocognitive impairment in exhibiting hemodynamic disturbance without stroke.
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TopBP1 and Claspin contribute to the radioresistance of lung cancer brain metastases.
Mol. Cancer
PUBLISHED: 05-11-2014
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Radiation therapy is one of the most effective therapeutic tools for brain metastasis. However, it is inevitable that some cancer cells become resistant to radiation. This study is focused on the identification of genes associated with radioresistance in metastatic brain tumor from lung cancer and the functional examination of the selected genes with regards to altered sensitivity of cancer cells to radiation.
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Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
Nicholas J Kassebaum, Amelia Bertozzi-Villa, Megan S Coggeshall, Katya A Shackelford, Caitlyn Steiner, Kyle R Heuton, Diego Gonzalez-Medina, Ryan Barber, Chantal Huynh, Daniel Dicker, Tara Templin, Timothy M Wolock, Ayse Abbasoglu Ozgoren, Foad Abd-Allah, Semaw Ferede Abera, Ibrahim Abubakar, Tom Achoki, Ademola Adelekan, Zanfina Ademi, Arsène Kouablan Adou, José C Adsuar, Emilie E Agardh, Dickens Akena, Deena Alasfoor, Zewdie Aderaw Alemu, Rafael Alfonso-Cristancho, Samia Alhabib, Raghib Ali, Mazin J Al Kahbouri, François Alla, Peter J Allen, Mohammad A AlMazroa, Ubai Alsharif, Elena Alvarez, Nelson Alvis-Guzmán, Adansi A Amankwaa, Azmeraw T Amare, Hassan Amini, Walid Ammar, Carl A T Antonio, Palwasha Anwari, Johan Arnlöv, Valentina S Arsic Arsenijevic, Ali Artaman, Majed Masoud Asad, Rana J Asghar, Reza Assadi, Lydia S Atkins, Alaa Badawi, Kalpana Balakrishnan, Arindam Basu, Sanjay Basu, Justin Beardsley, Neeraj Bedi, Tolesa Bekele, Michelle L Bell, Eduardo Bernabé, Tariku J Beyene, Zulfiqar Bhutta, Aref Bin Abdulhak, Jed D Blore, Berrak Bora Basara, Dipan Bose, Nicholas Breitborde, Rosario Cárdenas, Carlos A Castañeda-Orjuela, Ruben Estanislao Castro, Ferrán Catalá-López, Alanur Cavlin, Jung-Chen Chang, Xuan Che, Costas A Christophi, Sumeet S Chugh, Massimo Cirillo, Samantha M Colquhoun, Leslie Trumbull Cooper, Cyrus Cooper, Iuri da Costa Leite, Lalit Dandona, Rakhi Dandona, Adrian Davis, Anand Dayama, Louisa Degenhardt, Diego De Leo, Borja del Pozo-Cruz, Kebede Deribe, Muluken Dessalegn, Gabrielle A deVeber, Samath D Dharmaratne, Ugur Dilmen, Eric L Ding, Rob E Dorrington, Tim R Driscoll, Sergei Petrovich Ermakov, Alireza Esteghamati, Emerito Jose A Faraon, Farshad Farzadfar, Manuela Mendonca Felicio, Seyed-Mohammad Fereshtehnejad, Graça Maria Ferreira De Lima, Mohammad H Forouzanfar, Elisabeth B França, Lynne Gaffikin, Ketevan Gambashidze, Fortuné Gbètoho Gankpé, Ana C Garcia, Johanna M Geleijnse, Katherine B Gibney, Maurice Giroud, Elizabeth L Glaser, Ketevan Goginashvili, Philimon Gona, Dinorah González-Castell, Atsushi Goto, Hebe N Gouda, Harish Chander Gugnani, Rahul Gupta, Rajeev Gupta, Nima Hafezi-Nejad, Randah Ribhi Hamadeh, Mouhanad Hammami, Graeme J Hankey, Hilda L Harb, Rasmus Havmoeller, Simon I Hay, Ileana B Heredia Pi, Hans W Hoek, H Dean Hosgood, Damian G Hoy, Abdullatif Husseini, Bulat T Idrisov, Kaire Innos, Manami Inoue, Kathryn H Jacobsen, Eiman Jahangir, Sun Ha Jee, Paul N Jensen, Vivekanand Jha, Guohong Jiang, Jost B Jonas, Knud Juel, Edmond Kato Kabagambe, Haidong Kan, Nadim E Karam, André Karch, Corine Kakizi Karema, Anil Kaul, Norito Kawakami, Konstantin Kazanjan, Dhruv S Kazi, Andrew H Kemp, André Pascal Kengne, Maia Kereselidze, Yousef Saleh Khader, Shams Eldin Ali Hassan Khalifa, Ejaz Ahmed Khan, Young-Ho Khang, Luke Knibbs, Yoshihiro Kokubo, Soewarta Kosen, Barthélemy Kuate Defo, Chanda Kulkarni, Veena S Kulkarni, G Anil Kumar, Kaushalendra Kumar, Ravi B Kumar, Gene Kwan, Taavi Lai, Ratilal Lalloo, Hilton Lam, Van C Lansingh, Anders Larsson, Jong-Tae Lee, James Leigh, Mall Leinsalu, Ricky Leung, Xiaohong Li, Yichong Li, Yongmei Li, Juan Liang, Xiaofeng Liang, Stephen S Lim, Hsien-Ho Lin, Steven E Lipshultz, Shiwei Liu, Yang Liu, Belinda K Lloyd, Stephanie J London, Paulo A Lotufo, Jixiang Ma, Stefan Ma, Vasco Manuel Pedro Machado, Nana Kwaku Mainoo, Marek Majdan, Christopher Chabila Mapoma, Wagner Marcenes, Melvin Barrientos Marzan, Amanda J Mason-Jones, Man Mohan Mehndiratta, Fabiola Mejia-Rodriguez, Ziad A Memish, Walter Mendoza, Ted R Miller, Edward J Mills, Ali H Mokdad, Glen Liddell Mola, Lorenzo Monasta, Jonathan de la Cruz Monis, Julio Cesar Montañez Hernandez, Ami R Moore, Maziar Moradi-Lakeh, Rintaro Mori, Ulrich O Mueller, Mitsuru Mukaigawara, Aliya Naheed, Kovin S Naidoo, Devina Nand, Vinay Nangia, Denis Nash, Chakib Nejjari, Robert G Nelson, Sudan Prasad Neupane, Charles R Newton, Marie Ng, Mark J Nieuwenhuijsen, Muhammad Imran Nisar, Sandra Nolte, Ole F Norheim, Luke Nyakarahuka, In-Hwan Oh, Takayoshi Ohkubo, Bolajoko O Olusanya, Saad B Omer, John Nelson Opio, Orish Ebere Orisakwe, Jeyaraj D Pandian, Christina Papachristou, Jae-Hyun Park, Angel J Paternina Caicedo, Scott B Patten, Vinod K Paul, Boris Igor Pavlin, Neil Pearce, David M Pereira, Konrad Pesudovs, Max Petzold, Dan Poenaru, Guilherme V Polanczyk, Suzanne Polinder, Dan Pope, Farshad Pourmalek, Dima Qato, D Alex Quistberg, Anwar Rafay, Kazem Rahimi, Vafa Rahimi-Movaghar, Sajjad Ur Rahman, Murugesan Raju, Saleem M Rana, Amany Refaat, Luca Ronfani, Nobhojit Roy, Tania Georgina Sánchez Pimienta, Mohammad Ali Sahraian, Joshua A Salomon, Uchechukwu Sampson, Itamar S Santos, Monika Sawhney, Felix Sayinzoga, Ione J C Schneider, Austin Schumacher, David C Schwebel, Soraya Seedat, Sadaf G Sepanlou, Edson E Servan-Mori, Marina Shakh-Nazarova, Sara Sheikhbahaei, Kenji Shibuya, Hwashin Hyun Shin, Ivy Shiue, Inga Dora Sigfusdottir, Donald H Silberberg, Andrea P Silva, Jasvinder A Singh, Vegard Skirbekk, Karen Sliwa, Sergey S Soshnikov, Luciano A Sposato, Chandrashekhar T Sreeramareddy, Konstantinos Stroumpoulis, Lela Sturua, Bryan L Sykes, Karen M Tabb, Roberto Tchio Talongwa, Feng Tan, Carolina Maria Teixeira, Eric Yeboah Tenkorang, Abdullah Sulieman Terkawi, Andrew L Thorne-Lyman, David L Tirschwell, Jeffrey A Towbin, Bach X Tran, Miltiadis Tsilimbaris, Uche S Uchendu, Kingsley N Ukwaja, Eduardo A Undurraga, Selen Begüm Uzun, Andrew J Vallely, Coen H van Gool, Tommi J Vasankari, Monica S Vavilala, N Venketasubramanian, Salvador Villalpando, Francesco S Violante, Vasiliy Victorovich Vlassov, Theo Vos, Stephen Waller, Haidong Wang, Linhong Wang, Xiaorong Wang, Yanping Wang, Scott Weichenthal, Elisabete Weiderpass, Robert G Weintraub, Ronny Westerman, James D Wilkinson, Solomon Meseret Woldeyohannes, John Q Wong, Muluemebet Abera Wordofa, Gelin Xu, Yang C Yang, Yuichiro Yano, Gokalp Kadri Yentur, Paul Yip, Naohiro Yonemoto, Seok-Jun Yoon, Mustafa Z Younis, Chuanhua Yu, Kim Yun Jin, Maysaa El Sayed Zaki, Yong Zhao, Yingfeng Zheng, Maigeng Zhou, Jun Zhu, Xiao Nong Zou, Alan D Lopez, Mohsen Naghavi, Christopher J L Murray, Rafael Lozano.
Lancet
PUBLISHED: 05-02-2014
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The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
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Tpl2 induces castration resistant prostate cancer progression and metastasis.
Int. J. Cancer
PUBLISHED: 04-22-2014
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Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC.
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A Suggestion of Modified Classification of Trigeminal Schwannomas According to Location, Shape, and Extension.
Brain Tumor Res Treat
PUBLISHED: 04-21-2014
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Comprehensive knowledge of the anatomical features of trigeminal schwannomas (TSs) is essential in planning surgery to achieve complete tumor resection. In the current report, we propose a modified classification of TSs according to their location of origin, shape, and extension into the adjacent compartment, and discuss appropriate surgical strategies with this classification.
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High-Throughput, Miniaturized Clonogenic Analysis of a Limiting Dilution Assay on a Micropillar/Microwell Chip with Brain Tumor Cells.
Small
PUBLISHED: 04-18-2014
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The limiting dilution assay (LDA) is a clonogenic drug efficacy test designed to determine a value for drug efficacy based on an all-or-none (positive or negative) response within replicates. It also attempts to calculate minimum cell numbers for cells to form colony in each drugged conditions, wherein a large value implies high drug efficacy (as a large number of extant cells are required to start a colony). However, traditional LDAs are time-consuming to set up, often requiring many replicates for statistical analysis, and manual colony identification under a microscope to determine a positive or negative response is tedious and is susceptible to human error. To address these issues, a high-throughput miniaturized LDA assay is developed using a micropillar/microwell chip platform using an automatic colony identification method. Three glioblastoma multiforme (GBM) brain tumor isolates (448T, 464T, and 775T) are used to test this new assay, using the c-Met kinase inhibitors SU11274 and PHA665752 as the target drugs. The results show that the minimum cell number of 775T is larger than that of the other two cell types (SU11274 and PHA665752) in both the sampled drugs, a result that is in good agreement with the results of previous conventional experiments using 96 well plates.
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Supratentorial Extraventricular Anaplastic Ependymoma Presenting with Repeated Intratumoral Hemorrhage.
Brain Tumor Res Treat
PUBLISHED: 04-15-2014
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Supratentorial extraventricular anaplastic ependymomas are extremely rare. We report the case of a 23-year-old male with a supratentorial extraventricular anaplastic ependymoma that presented with repeated intratumoral hemorrhage. The patient was diagnosed with an intracerebral hematoma in the left occipital lobe and underwent operation. The hematoma did not reveal tumor cells, but a new tumor grew in the same location 5 years later. Magnetic resonance imaging showed a tumor with intratumoral hemorrhage. The patient underwent the tumor resection. Intraoperative findings showed that the tumor had no continuity with the ventricle. Histopathological examinations confirmed an anaplastic ependymoma. The spinal evaluation was unremarkable, and radiotherapy was administered to the left occipital lobe. Four years later, the tumor recurred at the cervicomedullary junction and T8-T9 levels. This case demonstrates that anaplastic ependymomas should be included in the differential diagnoses of supratentorial extraventricular tumors presenting with repeated intratumoral hemorrhage.
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Patterns of somatic alterations between matched primary and metastatic colorectal tumors characterized by whole-genome sequencing.
Genomics
PUBLISHED: 02-25-2014
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Colorectal cancer (CRC) patients have poor prognosis after formation of distant metastasis. Understanding the molecular mechanisms by which genetic changes facilitate metastasis is critical for the development of targeted therapeutic strategies aimed at controlling disease progression while minimizing toxic side effects. A comprehensive portrait of somatic alterations in CRC and the changes between primary and metastatic tumors has yet to be developed. We performed whole genome sequencing of two primary CRC tumors and their matched liver metastases. By comparing to matched germline DNA, we catalogued somatic alterations at multiple scales, including single nucleotide variations, small insertions and deletions, copy number aberrations and structural variations in both the primary and matched metastasis. We found that the majority of these somatic alterations are present in both sites. Despite the overall similarity, several de novo alterations in the metastases were predicted to be deleterious, in genes including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and progression of distant metastasis. Through careful examination of the mutation prevalence among tumor cells at each site, we also proposed distinct clonal evolution patterns between primary and metastatic tumors in the two cases. These results suggest that somatic alterations may play an important role in driving the development of colorectal cancer metastasis and present challenges and opportunities when considering the choice of treatment.
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Clinical significance of radiological stability in reconstructed thoracic and lumbar spine following vertebral body resection.
J Korean Neurosurg Soc
PUBLISHED: 02-18-2014
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Vertebral body replacement following corpectomy in thoracic or lumbar spine is performed with titanium mesh cage (TMC) containing any grafts. Radiological changes often occur on follow-up. This study investigated the relationship between the radiological stability and clinical symptoms.
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Efficacy of postoperative radiotherapy for high grade meningiomas.
J. Neurooncol.
PUBLISHED: 01-29-2014
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The necessity of postoperative radiotherapy (PORT) for meningiomas remains contentious. Here, the role of PORT in patients who underwent surgical resection for WHO grade II and III meningiomas was assessed. The record of 114 patients with WHO grade II (n = 72) and III (n = 42) meningiomas treated at Samsung Medical Center between March 1995 and April 2013 were reviewed and classified according to the extent of surgical resection and implementation of PORT. Median follow-up was 55.9 months. Simpson grade (SG) I, II, III, and IV resections were achieved in 29, 56, 9 and 20 patients, respectively. The 5-year local control (LC) and overall survival rate was 65.8 and 84.2 %, respectively. Thirty patients (26.3 %) developed local failure and five patients (4.4 %) developed distant metastases. The extent of surgical resection (SG I-II vs. III-IV) was influenced by tumor location (orbital and skull base lesions vs. others, p = 0.001) and the surgeons' experience (>10 operations, p = 0.044). Extent of surgical resection was also associated with local failure, overall progression, and overall survival (p = 0.001, p < 0.001, and p < 0.001, respectively). PORT improved LC in patients with incomplete surgical resection (SG III-IV, p = 0.049). Complete resection (SG I-II) is an important prognostic factor for LC and survival, and the extent of surgical resection (SG I-II vs. III-IV) is influenced by tumor location. PORT could improve the LC in WHO grade II-III meningioma patients who underwent incomplete surgical resection (SG III-IV).
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The neuroprotective effect of treatment with curcumin in acute spinal cord injury: laboratory investigation.
Neurol. Med. Chir. (Tokyo)
PUBLISHED: 01-28-2014
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The purpose of this study was investigating the effects of curcumin on the histological changes and functional recovery following spinal cord injury (SCI) in a rat model. Following either sham operation or SCI, 36 male Sprague-Dawley rats were distributed into three groups: sham group, curcumin-treated group, and vehicle-injected group. Locomotor function was assessed according to the Basso, Beattie, and Bresnahan (BBB) scale in rats who had received daily intraperitoneal injections of 200 mg/kg curcumin or an equivalent volume of vehicle for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation. BBB scores were significantly higher in rats receiving curcumin than receiving vehicle (P < 0.05). The cavity volume was significantly reduced in the curcumin group as compared to the control group (P = 0.039). Superoxide dismutase (SOD) activity was significantly elevated in the curcumin group as compared to the vehicle group but was not significantly different from the sham group (P < 0.05, P > 0.05, respectively) at one and two weeks after SCI. Malondialdehyde (MDA) levels were significantly elevated in the vehicle group as compared to the sham group (P < 0.05 at 1 and 2 weeks). MDA activity was significantly reduced in the curcumin group at 2 weeks after SCI when compared to the vehicle group (P = 0.004). The numbers of macrophage were significantly decreased in the curcumin group (P = 0.001). This study demonstrated that curcumin enhances early functional recovery after SCI by diminishing cavitation volume, anti-inflammatory reactions, and antioxidant activity.
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Targeting the epithelial to mesenchymal transition in glioblastoma: the emerging role of MET signaling.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Glioblastoma multiforme (GBM) is the most common human primary brain malignancy and has a dismal prognosis. Aggressive treatments using maximal surgical resection, radiotherapy, and temozolomide result in median survival of only 14.6 months in patients with GBM. Numerous clinical approaches using small molecule inhibitors have shown disappointing results because of the genetic heterogeneity of GBM. The epithelial to mesenchymal transition (EMT) is a crucial biological process occurring in the early development stages of many species. However, cancer cells often obtain the ability to invade and metastasize through the EMT, which triggers the scattering of cells. The hepatocyte growth factor (HGF)/MET signaling pathway is indicative of the EMT during both embryogenesis and the invasive growth of tumors, because HGF potently induces mesenchymal transition in epithelial-driven cells. Activation of MET signaling or co-overexpression of HGF and MET frequently represents aggressive growth and poor prognosis of various cancers, including GBM. Thus, efforts to treat cancers by inhibiting MET signaling using neutralizing antibodies or small molecule inhibitors have progressed during the last decade. In this review, we discuss HGF/MET signaling in the development of diseases, including cancers, as well as updates on MET inhibition therapy.
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Translational validation of personalized treatment strategy based on genetic characteristics of glioblastoma.
PLoS ONE
PUBLISHED: 01-01-2014
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Glioblastoma (GBM) heterogeneity in the genomic and phenotypic properties has potentiated personalized approach against specific therapeutic targets of each GBM patient. The Cancer Genome Atlas (TCGA) Research Network has been established the comprehensive genomic abnormalities of GBM, which sub-classified GBMs into 4 different molecular subtypes. The molecular subtypes could be utilized to develop personalized treatment strategy for each subtype. We applied a classifying method, NTP (Nearest Template Prediction) method to determine molecular subtype of each GBM patient and corresponding orthotopic xenograft animal model. The models were derived from GBM cells dissociated from patient's surgical sample. Specific drug candidates for each subtype were selected using an integrated pharmacological network database (PharmDB), which link drugs with subtype specific genes. Treatment effects of the drug candidates were determined by in vitro limiting dilution assay using patient-derived GBM cells primarily cultured from orthotopic xenograft tumors. The consistent identification of molecular subtype by the NTP method was validated using TCGA database. When subtypes were determined by the NTP method, orthotopic xenograft animal models faithfully maintained the molecular subtypes of parental tumors. Subtype specific drugs not only showed significant inhibition effects on the in vitro clonogenicity of patient-derived GBM cells but also synergistically reversed temozolomide resistance of MGMT-unmethylated patient-derived GBM cells. However, inhibitory effects on the clonogenicity were not totally subtype-specific. Personalized treatment approach based on genetic characteristics of each GBM could make better treatment outcomes of GBMs, although more sophisticated classifying techniques and subtype specific drugs need to be further elucidated.
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Angiographically documented cerebral vasospasm following transsphenoidal surgery for pituitary tumors.
Pituitary
PUBLISHED: 12-25-2013
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Symptomatic cerebral vasospasm (CVS) after transsphenoidal surgery (TSS) is very rare compared with vasospasm resulting from aneurysmal subarachnoid hemorrhage (SAH). Fewer than six cases documented by cerebral angiography have been reported. We evaluated the records of 15 patients in whom SAH developed after TSS. Their clinical symptoms, radiological and laboratory findings were analyzed. Among 15 patients with postoperative SAH, 11 did not show CVS during their postoperative course. However, four patients presented with various clinical symptoms suggestive of CVS on postoperative days 7-9. They showed an abrupt drop of serum sodium level 1 or 2 days before the onset of CVS symptoms. Patients with TSS-related SAH should be managed with proactive and aggressive treatment. Hyponatremia, which usually occurs around the first week after TSS, should not be ignored as a matter of metabolic or hormonal disequilibrium commonly encountered after pituitary surgery.
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Stereotactic radiosurgery for cerebellopontine angle meningiomas.
J. Neurosurg.
PUBLISHED: 12-13-2013
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Object To assess the long-term outcomes of stereotactic radiosurgery (SRS) for cerebellopontine angle (CPA) meningiomas, the authors retrospectively reviewed data from a 20-year experience. They evaluated progression-free survival as well as improvement, stabilization, or deterioration in clinical symptoms. Methods Seventy-four patients with CPA meningiomas underwent SRS involving various Gamma Knife technologies between 1990 and 2010. The most common presenting symptoms were dizziness or disequilibrium, hearing loss, facial sensory dysfunction, and headache. The median tumor volume was 3.0 cm(3) (range 0.3-17.1 cm(3)), and the median radiation dose to the tumor margin was 13 Gy (range 11-16 Gy). The median follow-up period was 40 months (range 4-147 months). Results At last imaging follow-up, the tumor volume had decreased in 46 patients (62%), remained stable in 26 patients (35%), and increased in 2 patients (3%). The progression-free survival after SRS was 98% at 1 year, 98% at 3 years, and 95% at 5 years. At the last clinical follow-up, 23 patients (31%) showed neurological improvement, 43 patients (58%) showed no change in symptoms or signs, and 8 patients (11%) had worsening symptoms or signs. The neurological improvement rate after SRS was 16% at 1 year, 31% at 3 years, and 40% at 5 years. The post-SRS deterioration rate was 5% at 1 year, 10% at 3 years, and 16% at 5 years. A multivariate analysis demonstrated that trigeminal neuralgia was the symptom most likely to worsen after SRS (HR 0.08, 95% CI 0.02-0.31; p = 0.001). Asymptomatic peritumoral edema occurred in 4 patients (5%) after SRS, and symptomatic adverse radiation effects developed in 7 patients (9%). Conclusions Stereotactic radiosurgery for CPA meningiomas provided a high tumor control rate and relatively low risk of ARE. Tumor compression of the trigeminal nerve by a CPA meningioma resulted in an increased rate of facial pain worsening in this patient experience.
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Hypofractionated intensity-modulated radiotherapy using simultaneous integrated boost technique with concurrent and adjuvant temozolomide for glioblastoma.
Tumori
PUBLISHED: 12-12-2013
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Aims and background. We assessed the therapeutic efficacy of combined hypofractionated intensity-modulated radiotherapy with temozolomide in patients with primary glioblastoma. Methods and study design. Thirty-nine patients with histologically confirmed glioblastoma were accrued. Using the simultaneous integrated boost technique, a dose of 50 Gy in 5-Gy fractions was applied to the gross tumor volume, together with 40 Gy in 4-Gy fractions and 30 Gy in 3-Gy fractions to the 1- and 2-cm margins from the gross tumor volume, respectively. Patients were also treated with concurrent temozolomide during intensity-modulated radiotherapy, followed by six cycles of adjuvant temozolomide. Results. Median follow-up was 16.8 months (range, 4.3-54.3). Tumor progression was observed in 28 patients (71.8%), and the median time to progression was 6.8 months. Median survival was 16.8 months, and it was affected significantly by the extent of surgery. During adjuvant temozolomide treatment, 3 patients (9.7%) developed grade 3-4 hematologic or hepatic toxicity. Radiation necrosis developed in 7 patients (17.9%) and massive necrosis, requiring emergency surgery, in 1 patient (2.6%). Conclusions. The regimen of hypofractionated intensity-modulated radiotherapy with temozolomide showed a relatively good outcome in patients with glioblastoma. Further studies are required to define the optimal fraction size for glioblastoma using this highly sophisticated radiation technique.
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Genetically-engineered Human Neural Stem Cells with Rabbit Carboxyl Esterase Can Target CNS Lymphoma.
Anticancer Res.
PUBLISHED: 12-11-2013
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Despite advances in its treatment, CNS lymphoma remains a devastating disease. Taking advantage of the tumour-tropic properties of neural stem cells (NSCs) is a novel therapeutic strategy. To apply this strategy to the treatment of CNS lymphoma, we investigated the role of NSCs expressing carboxyl esterase (HB1.F3.CE), which activates irinotecan.
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High-Throughput Screening (HTS) of Anticancer Drug Efficacy on a Micropillar/Microwell Chip Platform.
Anal. Chem.
PUBLISHED: 12-02-2013
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Contemporary cancer therapy refers to treatment based on genetic abnormalities found in patients tumor. However, this approach is faced with numerous challenges, including tumor heterogeneity and molecular evolution, insufficient tumor samples available along with genetic information linking to clinical outcomes, lack of therapeutic drugs containing pharmacogenomic information, and technical limitations of rapid drug efficacy tests with insufficient quantities of primary cancer cells from patients. To address these problems and improve clinical outcomes of current personalized gene-targeted cancer therapy, we have developed a micropillar/microwell chip platform, which is ideally suited for encapsulating primary cancer cells in nanoscale spots of hydrogels on the chip, generating efficacy data with various drugs, eventually allowing for a comparison of the in vitro data obtained from the chip with clinical data as well as gene expression data. As a proof of concept in this study, we have encapsulated a U251 brain cancer cell line and three primary brain cancer cells from patients (448T, 464T, and 775T) in 30 nL droplets of alginate and then tested the therapeutic efficacy of 24 anticancer drugs by measuring their dose responses. As a result, the IC50 values of 24 anticancer drugs obtained from the brain cancer cells clearly showed patient cell-specific efficacy, some of which were well-correlated with their oncogene overexpression (c-Met and FGFR1) as well as the in vivo previous results of the mouse xenograft model with the three primary brain cancer cells.
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Neuroprotective Benzyl Benzoate Glycosides from Disporum viridescens Roots in HT22 Hippocampal Neuronal Cells.
J. Nat. Prod.
PUBLISHED: 11-18-2013
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Bioassay-guided fractionation of the EtOAc extract from Disporum viridescens roots led to the isolation of five new benzyl benzoate glycosides, BBGs (1-5). The neuroprotective activities of the BBGs were screened using neuronal HT22 hippocampal cells. BBG-D (4) significantly protected murine hippocampal HT22 cells against glutamate-induced neurotoxicity by maintaining the antioxidative defense systems such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and the glutathione content. BBG-D, in a dose-and time-dependent manner, increased HO-1 expression through the selective activation of pERK signaling among the MAPK pathways. These results suggest that BBG-D could be a promising candidate for the treatment of neurodegenerative diseases related to glutamate-induced oxidative neuronal cytotoxicity.
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Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.
J. Surg. Res.
PUBLISHED: 10-11-2013
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Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples.
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Prevalence of and factors associated with osteoporosis among Korean cancer survivors: a cross-sectional analysis of the Fourth and Fifth Korea National Health and Nutrition Examination Surveys.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-03-2013
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Identifying and managing osteoporosis among cancer survivors is an important issue, yet little is known about the bone health of cancer survivors in Korea. This study was designed to measure the prevalence of osteoporosis and to assess related factors among Korean cancer survivors.
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Burden of disease attributable to the Hebei Spirit oil spill in Taean, Korea.
BMJ Open
PUBLISHED: 09-24-2013
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We aimed to assess the burden of disease (BOD) of the residents living in contaminated coastal area with oil spill and also analysed the BOD attributable to the oil spill by disease, age, sex and subregion.
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Switching strategy for mechanical thrombectomy of acute large vessel occlusion in the anterior circulation.
Stroke
PUBLISHED: 09-10-2013
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We introduce the concept of a switching strategy for mechanical thrombectomy with period-to-period analysis. In period 1, forced arterial suction thrombectomy with a Penumbra reperfusion catheter was performed, even in difficult cases; in period 2, forced arterial suction thrombectomy was initially performed, with switching to Solitaire in difficult cases.
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Alpha-smooth muscle actin (ACTA2) is required for metastatic potential of human lung adenocarcinoma.
Clin. Cancer Res.
PUBLISHED: 08-30-2013
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Metastatic relapse of primary lung cancer leads to therapeutic resistance and unfavorable clinical prognosis; therefore, identification of key molecules associated with metastatic conversion has significant clinical implications. We previously identified a link between early brain metastasis of lung adenocarcinoma and amplification of the ?-smooth muscle actin (ACTA2) gene. The aim of present study was to investigate the prognostic and functional significance of ACTA2 expression in cancer cells for the metastatic potential of lung adenocarcinomas.
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Tpl2 kinase impacts tumor growth and metastasis of clear cell renal cell carcinoma.
Mol. Cancer Res.
PUBLISHED: 08-27-2013
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Due to the innate high metastatic ability of renal cell carcinoma (RCC), many patients with RCC experience local or systemic relapses after surgical resection. A deeper understanding of the molecular pathogenesis underlying advanced RCC is essential for novel innovative therapeutics. Tumor progression locus 2 (Tpl2), upregulated in various tumor types, has been reported to be associated with oncogenesis and metastatic progression via activation of the MAPK signaling pathway. Herein, the relevance of Tpl2 in tumor growth and metastasis of RCC is explored. Inspection of The Cancer Genome Atlas (TCGA) indicated that Tpl2 overexpression was significantly related to the presence of metastases and poor outcome in clear cell RCC (ccRCC), which is the most aggressive subtype of RCC. Moreover, expression of Tpl2 and CXCR4 showed a positive correlation in ccRCC patients. Depletion of Tpl2 by RNAi or activity by a Tpl2 kinase inhibitor in human ccRCC cells remarkably suppressed MAPK pathways and impaired in vitro cell proliferation, clonogenicity, anoikis resistance, migration, and invasion capabilities. Similarly, orthotopic xenograft growth and lung metastasis were significantly inhibited by Tpl2 silencing. Furthermore, Tpl2 knockdown reduced CXCL12-directed chemotaxis and chemoinvasion accompanied with impaired downstream signaling, indicating potential involvement of Tpl2 in CXCR4-mediated metastasis. Taken together, these data indicate that Tpl2 kinase is associated with and contributes to disease progression of ccRCC. Implications: Tpl2 kinase activity has prognostic and therapeutic targeting potential in aggressive clear cell renal cell carcinoma.
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Glossiness representation using binocular color difference.
Opt Lett
PUBLISHED: 08-14-2013
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We demonstrate that a binocular color difference can be used to express the surface glossiness of an object on 3D display devices without being accompanied by a specular reflection pattern. A simple image with a binocular color difference provides a similar surface appearance impression to a real object that has the same binocular color difference. It is found that human binocular perception is likely to interpret binocular color difference as spectral reflectance rather than as transparency. Binocular glossiness is caused not only by a binocular lightness difference but also by a chromatic or hue difference.
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Where are We Now with Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Infarction?
J Cerebrovasc Endovasc Neurosurg
PUBLISHED: 07-12-2013
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In spite of the best medical treatment, large hemispheric infarction, resulting from acute occlusion of either the internal carotid or the proximal middle cerebral artery with insufficient collateral blood flow is associated with a high case fatality rate of approximately 60%. Thus, a decompressive hemicraniectomy is considered a life-saving procedure for this devastating disease. Findings of three recent randomized, controlled clinical trials and their meta-analysis showed that early surgical decompression not only reduced the number of case fatalities but also increased the incidence of favorable outcomes. The authors review the pathophysiology, historical background in previous studies, operative timing, surgical technique and clinical outcomes of surgical decompression for malignant hemispheric infarction.
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Gamma knife radiosurgery for brain metastases from breast cancer.
J Korean Neurosurg Soc
PUBLISHED: 06-26-2013
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The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS).
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Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction.
Nat. Chem. Biol.
PUBLISHED: 06-18-2013
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Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.
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Long-term changes in serum IGF-1 levels after successful surgical treatment of growth hormone-secreting pituitary adenoma.
Neurosurgery
PUBLISHED: 06-04-2013
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Successful treatment of acromegaly is known to normalize serum insulin-like growth factor 1 (IGF-1) levels within days after surgery. However, our clinical observations indicate that many cases of acromegaly show delayed normalization of serum IGF-1 levels after complete tumor resection.
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What is different about medical students interested in non-clinical careers?
BMC Med Educ
PUBLISHED: 05-28-2013
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The proportion of medical school graduates who pursue careers other than full-time clinical practice has increased in some countries as the physicians role has evolved and diversified with the changing landscape of clinical practice and the advancement of biomedicine. Still, past studies of medical students career choices have focused on clinical specialties and little is known about their choice of non-clinical careers. The present study examined backgrounds, motivation and perceptions of medical students who intended non-clinical careers.
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Intramedullary spinal cord metastasis in renal cell carcinoma: a case report of the surgical experience.
J. Korean Med. Sci.
PUBLISHED: 04-03-2013
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Intramedullary spinal cord metastasis (ISCM) from renal cell carcinoma (RCC) is rare manifestation and most of them are treated by adjuvant treatment modalities like radiotherapy. Despite the radio-resistance of RCC itself, focal radiotherapy has been preferred as the first-line treatment modality of ISCM from RCC and only a few cases underwent surgical treatment. We describe a case of ISCM from RCC, which underwent surgical excision and pathologically confirmed. A 44-yr-old man was presented with rapid deterioration of motor weakness during focal radiotherapy for ISCM from RCC. After the surgery for removal of the tumor mass and spinal cord decompression, his motor power was dramatically improved to ambulate by himself. We report the first published Korean case of ISCM from RCC confirmed pathologically and describe our surgical experience and his clinical characteristics.
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Permissive attitude toward suicide and future intent in individuals with and without depression: results from a nationwide survey in Korea.
J. Nerv. Ment. Dis.
PUBLISHED: 03-30-2013
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Many previous studies have revealed that individuals with depression have higher thought of suicide, although not always exhibiting intent. We investigated the associated factors with respect to intent for suicide in the future. A total of 1584 adults were selected through a nationwide multistage probability sampling, randomly one person per household, and through face-to-face interviews (response rate was 63.4%) using the suicidality module of the Mini-International Neuropsychiatric Interview and the Patient Health Questionnaire-9. The group with depression (n = 152) revealed a significantly higher level of future suicide intent (t = 4.65, p <0.0001) and permissive attitude (t = 4.32, p <0.0001) than did the group without depression, which regarded suicide as free from life suffering, a personal right, and a solution to a difficult situation. After adjusting for all variables in the multiple logistic regression models, permissive attitude (adjusted odds ratio, 3.69; 95% confidence interval, 1.97-6.89) was the only factor significantly associated with future suicide intent, whereas age; sex; education years; monthly income; financial, job, and family stress; physical illness; lifetime suicide attempt; and depression showed no statistical significance. The group with depression showed significantly higher levels of future suicide intent than did the group without depression in those who had a higher permissive attitude (t = 4.18, p <0.0001) but not in those who had lower permissive attitudes (t = 1.98, p = 0.067). Permissive attitude toward suicide was associated with intent for suicide in the future in individuals with depression. Permissive attitude could be evaluated and corrected to prevent suicide.
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Burden of disease due to dementia in the elderly population of Korea: present and future.
BMC Public Health
PUBLISHED: 03-27-2013
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With the rapid aging of populations around the world, dementia has become one of the most important public health problems in Eastern Asian countries. The purpose of the present study was to provide an estimate of the burden of dementia and forecast its future burden, as generalized to the Korean population, and to provide detailed gender- and age-specific information regarding the burden of dementia in the elderly population of Korea.
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A comparison of postoperative pain after conventional open thyroidectomy and transaxillary single-incision robotic thyroidectomy: a prospective study.
Ann. Surg. Oncol.
PUBLISHED: 03-26-2013
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The aim of this study was to compare conventional open thyroidectomy with robotic thyroidectomy in terms of postoperative pain.
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Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment.
Neurobiol. Aging
PUBLISHED: 03-22-2013
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Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB-positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment.
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Comparison of lumbopelvic rhythm and flexion-relaxation response between 2 different low back pain subtypes.
Spine
PUBLISHED: 03-22-2013
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A cross-sectional study to compare the kinematics and muscle activities during trunk flexion and return task in people with and without low back pain (LBP).
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Risk of seizure and its clinical implication in the patients with cerebral metastasis from lung cancer.
Acta Neurochir (Wien)
PUBLISHED: 03-18-2013
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The prevalence, risk factors, and clinical implication of seizure development were investigated in patients with metastatic brain tumors.
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Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment.
Ann. Neurol.
PUBLISHED: 03-12-2013
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Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment.
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F-18 fluorodeoxyglucose PET/CT and post hoc PET/MRI in a case of primary meningeal melanomatosis.
Korean J Radiol
PUBLISHED: 02-22-2013
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Primary meningeal melanomatosis is a rare, aggressive variant of primary malignant melanoma of the central nervous system, which arises from melanocytes within the leptomeninges and carries a poor prognosis. We report a case of primary meningeal melanomatosis in a 17-year-old man, which was diagnosed with (18)F-fluorodeoxyglucose (F-18 FDG) PET/CT, and post hoc F-18 FDG PET/MRI fusion images. Whole-body F-18 FDG PET/CT was helpful in ruling out the extracranial origin of melanoma lesions, and in assessing the therapeutic response. Post hoc PET/MRI fusion images facilitated the correlation between PET and MRI images and demonstrated the hypermetabolic lesions more accurately than the unenhanced PET/CT images. Whole body F-18 FDG PET/CT and post hoc PET/MRI images might help clinicians determine the best therapeutic strategy for patients with primary meningeal melanomatosis.
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Improving the performance of risk-adjusted mortality modeling for colorectal cancer surgery by combining claims data and clinical data.
J Prev Med Public Health
PUBLISHED: 02-19-2013
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The objective of this study was to evaluate the performance of risk-adjusted mortality models for colorectal cancer surgery.
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Burden of cancer in Korea during 2000-2020.
Cancer Epidemiol
PUBLISHED: 02-10-2013
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This study estimates the burden of cancer in Korea during 2000-2020, ameliorating the Global Burden of Disease Study Group (GBD) method with the Incidence-Prevalence-Mortality (IPM) Model.
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Prevalence of musculoskeletal symptoms related with activities of daily living and contributing factors in Korean adults.
J Prev Med Public Health
PUBLISHED: 01-31-2013
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This study aims to investigate the prevalence of musculoskeletal symptoms and factors related to daily activities in a representative Korean population.
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Application of low-field intraoperative magnetic resonance imaging in transsphenoidal surgery for pituitary adenomas: technical points to improve the visibility of the tumor resection margin.
Acta Neurochir (Wien)
PUBLISHED: 01-15-2013
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Intraoperative magnetic resonance imaging (iMRI) is proven to be advantageous in transsphenoidal surgery (TSS) for pituitary adenomas. We evaluated the efficacy of low-field iMRI. Also, we described several techniques to enhance the visibility of the tumor resection margin.
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Rescue strategy for acute carotid stent thrombosis during carotid stenting with distal filter protection using forced arterial suction thrombectomy with a reperfusion catheter of the Penumbra System: a technical note.
Acta Neurochir (Wien)
PUBLISHED: 01-11-2013
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Among the procedural complications related to carotid artery stenting (CAS), internal carotid artery (ICA) flow arrest is one of the most drastic complications, as it can cause major ischemic stroke. Acute carotid stent thrombosis (ACST) is a rare etiology of ICA flow arrest during carotid artery stenting with distal filter protection, but the most devastating. Moreover, no definitive management strategy has been established so far for treating ACST.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.