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Find video protocols related to scientific articles indexed in Pubmed.
Effect of the Novel BKCa Channel Opener LDD175 on the Modulation of Corporal Smooth Muscle Tone.
J Sex Med
PUBLISHED: 11-12-2014
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The BKCa channel has been reported to play an important role in erectile function. Recently, novel BKCa channel activator, LDD175, was introduced.
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Asymmetric Pectus Excavatum Is Associated with Overgrowth of Ribs Rather Than Cartilage.
Thorac Cardiovasc Surg
PUBLISHED: 11-11-2014
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Background?To evaluate whether the overgrowth of costal cartilage exists in patients with pectus excavatum, we compared the length of the costal cartilage and ribs between patients with asymmetric pectus excavatum and controls without chest wall deformity using three-dimensional computed tomography. Materials and Methods?Nineteen adult patients with asymmetric pectus excavatum and 19 age and sex matched controls without chest wall deformity were enrolled. We measured the full lengths of the fourth to sixth ribs and costal cartilage using three-dimensional volume-rendered computed tomography images and curved multiplanar reformatting techniques. The lengths of ribs and costal cartilage, their summations, and the costal index ([length of cartilage/length of rib]?×?100 [%]) were compared on the asymmetrically depressed side of patients (Group A), the opposite side of the same patients (Group B), and controls (Group C) at the fourth to sixth levels. Results?The lengths of the ribs of groups A and B were significantly longer (p??0.05) among the three groups (53.1?±?7.3?mm vs. 54.6?±?8.6?mm vs. 52.9?±?5.2 at the fourth level, 71.9?±?9.6?mm vs. 72.3?±?9.9?mm vs. 69.2?±?7.1?mm at the fifth level, and 100.1?±?15.2?mm vs. 104.2?±?15.8?mm vs. 99.1?±?9.1?mm at sixth level). The summations of the rib and costal cartilage lengths were longer in groups A and B than in group C. The costal indices were not different among the three groups at the fourth, fifth, and sixth rib levels. Conclusion?In patients who had asymmetric pectus excavatum with a???21-degree angle of sternal rotations, the ribs but not the costal cartilage were longer than those of controls. These findings suggest that cartilage overgrowth is not the main factor responsible for asymmetric pectus excavatum, and it could instead be related to abnormal rib growth.
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Considerations for radiation therapy in hepatocellular carcinoma: the radiation oncologists' perspective.
Dig Dis
PUBLISHED: 10-29-2014
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Although the Barcelona Clinic Liver Cancer staging system does not recommend radiation therapy (RT) as a locoregional modality in hepatocellular carcinoma (HCC), many prospective and retrospective studies have reported excellent local control with favorable survival rates after RT using modern techniques. Additionally, there have been several comparative or meta-analysis results reporting the superiority of RT in unresectable HCC. Therefore, it might be more reasonable to apply RT in unresectable HCC as an alternative locoregional modality to improve local control in HCC. However, several considerations for the application of RT in HCC exist. The considerations for RT in HCC are purpose, combination treatment and technique. The purpose of RT should be based on baseline liver status as well as tumor extent and location. There are several reasonable advantages in local, intrahepatic and extrahepatic control when combined with other modalities, but it could lead to overtreatment in some cases. The technical considerations according to the purpose and combination modality are the final step. For the application of RT in HCC, the purpose of RT, combination strategy and technical considerations should be taken into account. © 2014 S. Karger AG, Basel.
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18F-Fluorodeoxyglucose and 11C-methionine positron emission tomography in relation to methyl-guanine methyltransferase promoter methylation in high-grade gliomas.
Nucl Med Commun
PUBLISHED: 10-24-2014
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Methylation status of the methyl-guanine methyltransferase (MGMT) promoter is associated with a favorable response to a DNA alkylating agent in high-grade gliomas. We analyzed PET scans of patients with high-grade gliomas to determine whether the MGMT methylation status affects the tumor metabolic characteristics.
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Glioblastoma Treated with Concurrent Radiation Therapy and Temozolomide Chemotherapy: Differentiation of True Progression from Pseudoprogression with Quantitative Dynamic Contrast-enhanced MR Imaging.
Radiology
PUBLISHED: 10-22-2014
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Purpose To explore the role of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the differentiation of true progression from pseudoprogression in patients with glioblastoma on the basis of findings in entirely newly developed or enlarged enhancing lesions after concurrent radiation therapy and chemotherapy with temozolomide and to evaluate the diagnostic performance of the quantitative pharmacokinetic parameters obtained at dynamic contrast-enhanced MR imaging, such as the volume transfer constant ( K(trans) volume transfer constant ), the extravascular extracellular space per unit volume of tissue( ve extravascular extracellular space per unit volume of tissue ), and the blood plasma volume per unit volume of tissue( vp blood plasma volume per unit volume of tissue ). Materials and Methods This prospective study had institutional review board approval; written informed consent was obtained from all patients. Thirty-three patients with histopathologically proven glioblastoma who had undergone concurrent radiation therapy and chemotherapy with temozolomide were included. Dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters, including K(trans) volume transfer constant , ve extravascular extracellular space per unit volume of tissue , and vp blood plasma volume per unit volume of tissue , were calculated for newly developed or enlarged enhancing lesions. Pharmacokinetic parameters were compared between the true progression (n = 17) and pseudoprogression (n = 16) groups by using unpaired t tests and then multivariable analysis. Results The mean K(trans) volume transfer constant and ve extravascular extracellular space per unit volume of tissue were higher in the true progression group than in the pseudoprogression group (mean K(trans) volume transfer constant , 0.44 min(-1) ± 0.25 [standard deviation] and 0.23 min(-1) ± 0.10 for true progression and pseudoprogression groups, respectively, P = .004; and mean ve extravascular extracellular space per unit volume of tissue , 1.26 ± 0.78 and 0.75 ± 0.49 for true progression and pseudoprogression groups, respectively, P = .034). Multivariable analysis showed that mean K(trans) volume transfer constant was the only independently differentiating variable (P = .004). Conclusion Dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters, including K(trans) volume transfer constant and ve extravascular extracellular space per unit volume of tissue , in the entire newly developed or enlarged enhancing lesion may be useful objective diagnostic tools in the differentiation of true progression from pseudoprogression in patients with glioblastoma who have undergone concurrent radiation therapy and chemotherapy with temozolomide. © RSNA, 2014.
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A Simple Method for the Assessment of Fusarium Head Blight Resistance in Korean Wheat Seedlings Inoculated with Fusarium graminearum.
Plant Pathol. J.
PUBLISHED: 10-08-2014
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Fusarium head blight (FHB; scab) caused mainly by Fusarium graminearum is a devastating disease of wheat and barley around the world. FHB causes yield reductions and contamination of grain with trichothecene mycotoxins such as deoxynivalenol (DON) which are a major health concern for humans and animals. The objective of this research was to develop an easy seed or seedling inoculation assay, and to compare these assays with whole plant resistance of twenty-nine Korean winter wheat cultivars to FHB. The clip-dipping assay consists of cutting off the coleoptiles apex, dipping the coleoptiles apex in conidial suspension, covering in plastic bag for 3 days, and measuring the lengths of lesions 7 days after inoculation. There were significant cultivar differences after inoculation with F. graminearum in seedling relative to the controls. Correlation coefficients between the lesion lengths of clip-dipping inoculation and FHB Type II resistance from adult plants were significant (r=0.45; P<0.05). Results from two other seedling inoculation methods, spraying and pin-point inoculation, were not correlated with adult FHB resistance. Single linear correlation was not significant between seed germination assays (soaking and soak-dry) and FHB resistance (Type I and Type II), respectively. These results showed that clip-dipping inoculation method using F. graminearum may offer a real possibility of simple, rapid, and reliable for the early screening of FHB resistance in wheat.
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Restoration of cellular ubiquitin reverses impairments in neuronal development caused by disruption of the polyubiquitin gene Ubb.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-20-2014
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Disruption of the polyubiquitin gene Ubb leads to hypothalamic neurodegeneration and metabolic disorders, including obesity and sleep abnormalities, in mice. However, it has yet to be determined whether or not these neural phenotypes in Ubb(-/-) mice are directly caused by cell autonomous defects in maintaining proper levels of ubiquitin (Ub). To directly demonstrate that reduced levels of Ub are sufficient to cause neuronal abnormalities, we investigated the characteristics of cultured neurons isolated from Ubb(-/-) mouse embryonic brains. We found that neuronal morphology, neurite outgrowth, and synaptic development were significantly impaired in Ubb(-/-) neurons. Furthermore, we observed the growth of astrocytes in Ubb(-/-) cell cultures despite the fact that cells were cultured under conditions promoting neuronal growth. When the reduced levels of free Ub, but not Ub conjugates, in Ubb(-/-) cells were restored to those of wild-type cells by providing exogenous Ub via lentivirus-mediated delivery, the increased apoptosis observed in Ubb(-/-) cells was almost completely abolished. Ectopic expression of Ub also improved neuronal and glial phenotypes observed in Ubb(-/-) cells. Therefore, our study suggests that Ub homeostasis, or the maintenance of cellular free Ub above certain threshold levels, is essential for proper neuronal development and survival.
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Disruption of polyubiquitin gene Ubb causes dysregulation of neural stem cell differentiation with premature gliogenesis.
Sci Rep
PUBLISHED: 09-15-2014
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Disruption of polyubiquitin gene Ubb leads to early-onset reactive gliosis and adult-onset hypothalamic neurodegeneration in mice. However, it remains unknown why reduced levels of ubiquitin (Ub) due to loss of Ubb lead to these neural phenotypes. To determine whether or not the defects in neurons or their progenitors per se, but not in their cellular microenvironment, are the cause of the neural phenotypes observed in Ubb(-/-) mice, we investigated the properties of cultured cells isolated from Ubb(-/-) mouse embryonic brains. Although cells were cultured under conditions promoting neuronal growth, Ubb(-/-) cells underwent apoptosis during culture in vitro, with increased numbers of glial cells and decreased numbers of neurons. Intriguingly, at the beginning of the Ubb(-/-) cell culture, the number of neural stem cells (NSCs) significantly decreased due to their reduced proliferation and their premature differentiation into glial cells. Furthermore, upregulation of Notch target genes due to increased steady-state levels of Notch intracellular domain (NICD) led to the dramatic reduction of proneuronal gene expression in Ubb(-/-) cells, resulting in inhibition of neurogenesis and promotion of gliogenesis. Therefore, our study suggests an unprecedented role for cellular Ub pools in determining the fate and self-renewal of NSCs.
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MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix.
World J Surg Oncol
PUBLISHED: 09-11-2014
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MicroRNA (miRNA) expression is known to be deregulated in cervical carcinomas. However, no data is available about the miRNA expression pattern for the minimal deviation adenocarcinoma (MDA) of uterine cervix. We sought to detect deregulated miRNAs in MDA in an attempt to find the most dependable miRNA or their combinations to understand their tumorigenesis pathway and to identify diagnostic or prognostic biomarkers. We also investigated the association between those miRNAs and their target genes, especially Notch1 and Notch2.
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Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial.
Lancet Oncol.
PUBLISHED: 09-04-2014
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The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy.
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Multicenter validation study of a prognostic index for portal vein tumor thrombosis in hepatocellular carcinoma.
Cancer Res Treat
PUBLISHED: 07-19-2014
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We previously reported on a staging system and prognostic index (PITH) for portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT) at a single institution. The aim of this study is to validate the PITH staging system using data from patients at other institutions and to compare it with other published staging systems.
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Outcome of Local Excision Following Preoperative Chemoradiotherapy for Clinically T2 Distal Rectal Cancer: A Multicenter Retrospective Study (KROG 12-06).
Cancer Res Treat
PUBLISHED: 07-15-2014
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The aim of this study was to examine the clinical implications of a pathologically complete response after neoadjuvant chemoradiotherapy (CRT) followed by local excision for patients with cT2 rectal cancer who refused radical surgery.
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Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population.
Psychiatr. Genet.
PUBLISHED: 07-12-2014
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Located on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia. In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.
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Functional effects of a pathogenic mutation in Cereblon (CRBN) on the regulation of protein synthesis via the AMPK-mTOR cascade.
J. Biol. Chem.
PUBLISHED: 07-03-2014
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Initially identified as a protein implicated in human mental deficit, cereblon (CRBN) was recently recognized as a negative regulator of adenosine monophosphate-activated protein kinase (AMPK) in vivo and in vitro. Here, we present results showing that CRBN can effectively regulate new protein synthesis through the mammalian target of rapamycin (mTOR) signaling pathway, a downstream target of AMPK. Whereas deficiency of Crbn repressed protein translation via activation of the AMPK-mTOR cascade in Crbn-knock-out mice, ectopic expression of the wild-type CRBN increased protein synthesis by inhibiting endogenous AMPK. Unlike the wild-type CRBN, a mutant CRBN found in human patients, which lacks the last 24 amino acids, failed to rescue mTOR-dependent repression of protein synthesis in Crbn-deficient mouse fibroblasts. These results provide the first evidence that Crbn can activate the protein synthesis machinery through the mTOR signaling pathway by inhibiting AMPK. In light of the fact that protein synthesis regulated by mTOR is essential for various forms of synaptic plasticity that underlie the cognitive functions of the brain, the results of this study suggest a plausible mechanism for CRBN involvement in higher brain function in humans, and they may help explain how a specific mutation in CRBN can affect the cognitive ability of patients.
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Prediction of pathologic staging with magnetic resonance imaging after preoperative chemoradiotherapy in rectal cancer: Pooled analysis of KROG 10-01 and 11-02.
Radiother Oncol
PUBLISHED: 06-18-2014
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The reported overall accuracy of MRI in predicting the pathologic stage of nonirradiated rectal cancer is high. However, the role of MRI in restaging rectal tumors after neoadjuvant CRT is contentious. Thus, we evaluate the accuracy of restaging magnetic resonance imaging (MRI) for rectal cancer patients who receive preoperative chemoradiotherapy (CRT).
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Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma.
Oncotarget
PUBLISHED: 06-17-2014
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We investigated the role of somatic mutations and a common single nucleotide polymorphism (SNP) in the hTERT promoter region on hTERT expression and clinical outcomes. The hTERT promoter region was sequenced from 48 glioblastomas. hTERT expression was analyzed by quantitative real time-PCR. The association between hTERT promoter genetic changes and other genomic events and clinical variables common in gliomas were examined. C228T and C250T somatic mutations were found in 60.4% of glioblastomas, and a common SNP (T349C) was found in 66.6%. Somatic mutations and the SNP likely have opposing effects on hTERT expression. hTERT expression was significantly higher in the C228T or C250T mutated tumors. Tumors with the T349C genotype showed lower hTERT expression when C228T or C250T mutations were present. However, no significant survival differences were observed among the groups with or without hTERT promoter mutations and SNP. There was a significant association between genetic changes in the hTERT promoter and patient age as well as MGMT promoter methylation and EGFR amplification. hTERT expression is modulated by somatic mutations in the hTERT promoter as well as a common polymorphism. However, hTERT related genomic changes have limited value as an independent prognostic factor for clinical outcomes in glioblastomas.
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Pattern of care of anaplastic oligodendroglioma and oligoastrocytoma in a Korean population: the Korean radiation oncology group study 13-12.
J. Neurooncol.
PUBLISHED: 06-12-2014
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This study investigated the treatment of anaplastic oligodendroglial tumors across nine Korean institutions. We reviewed the medical records from 381 patients with histologically confirmed anaplastic oligodendroglioma or anaplastic oligoastrocytoma (AOA) from 2000 to 2010. Clinical factors and treatment patterns were analyzed for each year. Post-operative therapy was performed in 354 patients (94.1 %), of which 133 received radiotherapy (RT) alone and 189 received both RT and chemotherapy. RT alone was the preferred treatment toward the end of the study period (29.4 % in 2000-2001 vs. 56.3 % in 2010, P = 0.005). The use of procarbazine, lomustine, and vincristine (PCV) decreased (57.6 % in 2000-2001 vs. 28.6 % in 2010, P = 0.001) and the use of temozolomide (TMZ) increased (0 % in 2000-2001 vs. 61.9 % in 2010, P < 0.001) over the study period. A combination of chemotherapy and RT was used more often than RT alone in young patients (P = 0.036) and patients with a good performance status (P = 0.023). The 1p/19q co-deletion status and O-6-methyguanine-DNA methyltransferase methylation were analyzed since 2004 but were not significant factors for determining whether to administer chemotherapy. Among the patients who received chemotherapy, TMZ was used more often in patients with AOA (P = 0.007) and PCV was used more often in patients with either multiple lesions (P = 0.027) or the 1p/19q co-deletion (P = 0.026). Our results demonstrate that the treatment pattern for oligodendroglial tumors changed significantly across the study period. In particular, TMZ has replaced PCV, and the use of molecular markers as well as RT alone has increased, but a unified protocol remains to be established.
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Cellular ubiquitin pool dynamics and homeostasis.
BMB Rep
PUBLISHED: 06-12-2014
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Ubiquitin (Ub) is a versatile signaling molecule that plays important roles in a variety of cellular processes. Cellular Ub pools, which are composed of free Ub and Ub conjugates, are in dynamic equilibrium inside cells. In particular, increasing evidence suggests that Ub homeostasis, or the maintenance of free Ub above certain threshold levels, is important for cellular function and survival under normal or stress conditions. Accurate determination of various Ub species, including levels of free Ub and specific Ub chain linkages, have become possible in biological specimens as a result of the introduction of the proteomic approach using mass spectrometry. This technology has facilitated research on dynamic properties of cellular Ub pools and has provided tools for in-depth investigation of Ub homeostasis. In this review, we have also discussed the consequences of the disruption of Ub pool dynamics and homeostasis via deletion of polyubiquitin genes or mutations of deubiquitinating enzymes. The common consequence was a reduced availability of free Ub and a significant impact on the function and viability of cells. These observations further indicate that the levels of free Ub are important determinants for cellular protection.
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Preoperative weakness and demyelination of the corticospinal tract in meningioma patients : changes in diffusion parameters using diffusion tensor imaging.
J Korean Neurosurg Soc
PUBLISHED: 05-31-2014
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Differentiation of demyelination in white matter from axonal damage can be determined using diffusion tensor imaging (DTI). In this study using meningioma patients an attempt was made to evaluate the relationship between preoperative weakness and the changes of diffusion parameters in the corticospinal tract (CST) using DTI.
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Evaluation of extracellular volume fraction thresholds corresponding to myocardial late-gadolinium enhancement using cardiac magnetic resonance.
Int J Cardiovasc Imaging
PUBLISHED: 05-22-2014
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To establish extracellular volume fraction (ECV) thresholds corresponding to myocardial lesion detected by late-gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Fifty-six patients with myocardial infarction or hypertrophic cardiomyopathy underwent LGE, pre- and post-contrast modified Look-Locker inversion recovery (MOLLI) sequences on a 3-T CMR system. Short-axis MOLLI images generated ECV maps of left ventricular (LV) walls. The LGE areas were semi-automatically determined by different signal threshold techniques. The areas of elevated ECV were measured using ECV thresholds of 28-48 %. The LGE areas were compared with the areas of elevated ECV at the corresponding LV levels. The myocardial areas of LGE and elevated ECVs showed a strong and positive correlation (P < 0.01). The LGE threshold, set at two standard deviations above the mean signal from the remote myocardium, corresponded well with the area of ECV >32 %. When using the full width at half-maximum (FWHM) technique, the LGE area corresponded well with the area of ECV >42 or 44 %. By applying particular ECV thresholds, myocardial ECV maps can define myocardial status equivalent to LGE, and definite ECV thresholds may be useful for the straightforward evaluation of myocardial phenotypes.
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Prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases.
Radiat Oncol J
PUBLISHED: 05-13-2014
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To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases.
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Malignant glioma: MR imaging by using 5-aminolevulinic acid in an animal model.
Radiology
PUBLISHED: 05-12-2014
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To evaluate the use of 5-aminolevulinic acid (5-ALA) for the noninvasive detection of malignant gliomas by using in vivo magnetic resonance (MR) imaging in a mouse brain tumor model.
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Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea.
J. Korean Med. Sci.
PUBLISHED: 04-29-2014
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This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.
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Metabolomic comparison between cells over-expressing isocitrate dehydrogenase 1 and 2 mutants and the effects of an inhibitor on the metabolism.
J. Neurochem.
PUBLISHED: 04-28-2014
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The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have neomorphic activity of generating 2-hydroxyglutarate (2-HG) which has been implicated in the oncogenesis. Although similarities in structure and enzyme activity for the two isotypic mutations have been suggested, the difference in their cellular localization and biochemical properties suggests differential effects on the metabolic oncogenesis. Using U87 cells transfected with either wild-type (WT) and mutant (MT) IDH genes, the MT-IDH1 and MT-IDH2 cells were compared with NMR-based metabolomics. When normalized with the respective WT-IDH cells, the general metabolic shifts of MT-IDH1 and IDH2 were almost opposite. Subsequent analysis with LC-MS and metabolic pathway mapping showed that key metabolites in pentose phosphate pathway and tricarboxylic acid cycle are disproportionately altered in the two mutants, suggesting different activities in the key metabolic pathways. Notably, lactate level was lower in MT-IDH2 cells which produced more 2-HG than MT-IDH1 cells, indicating that the Warburg effects can be overridden by the production of 2-HG. We also found that the effect of a mutant enzyme inhibitor is mainly reduction of the 2-HG level rather than general metabolic normalization. Overall, the metabolic alterations in the MT-IDH1 and 2 can be different and seem to be commensurate with the degree of 2-HG production. The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2, respectively, (IDH1 and IDH2) have neomorphic activity of generating 2-hydroxyglutarate (2-HG) which has been implicated in oncogenesis. The mutant cell's metabolic shifts from the respective wild type cells were almost opposite, with lactate level being lower in the IDH2 mutant only, implicating an overridden Warburg effect. The metabolic effect of an IDH1 mutant inhibitor was limited to 2-HG lowering.
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Fate of pulmonary nodules detected by computer-aided diagnosis and physician review on the computed tomography simulation images for hepatocellular carcinoma.
Radiat Oncol J
PUBLISHED: 04-18-2014
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To investigate the frequency and clinical significance of detected incidental lung nodules found on computed tomography (CT) simulation images for hepatocellular carcinoma (HCC) using computer-aided diagnosis (CAD) and a physician review.
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Correlation of 11C-methionine PET and diffusion-weighted MRI: is there a complementary diagnostic role for gliomas?
Nucl Med Commun
PUBLISHED: 04-09-2014
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11C-Methionine (MET) PET and diffusion-weighted (DW) MRI are commonly used for evaluation of gliomas. We assessed the correlation between MET uptake and diffusion restriction measured on DW MRI in glioma.
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Ablation of cereblon attenuates myocardial ischemia-reperfusion injury.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-08-2014
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Cereblon (CRBN) was originally identified as a target protein for a mild type of mental retardation in humans. However, recent studies showed that CRBN acts as a negative regulator of AMP-activated protein kinase (AMPK) by binding directly to the AMPK catalytic subunit. Because AMPK is implicated in myocardial ischemia-reperfusion (I-R) injury, we reasoned that CRBN might play a role in the pathology of myocardial I-R through regulation of AMPK activity. To test this hypothesis, wild-type (WT) and crbn knockout (KO) mice were subjected to I-R (complete ligation of the coronary artery for 30 min followed by 24h of reperfusion). We found significantly smaller infarct sizes and less fibrosis in the hearts of KO mice than in those of WT mice. Apoptosis was also significantly reduced in the KO mice compared with that in WT mice, as shown by the reduced numbers of TUNEL-positive cells. In parallel, AMPK activity remained at normal levels in KO mice undergoing I-R, whereas it was significantly reduced in WT mice under the same conditions. In rat neonatal cardiomyocytes, overexpression of CRBN significantly reduced AMPK activity, as demonstrated by reductions in both phosphorylation levels of AMPK and the expression of its downstream target genes. Collectively, these data demonstrate that CRBN plays an important role in myocardial I-R injury through modulation of AMPK activity.
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HOXA10 is associated with temozolomide resistance through regulation of the homologous recombinant DNA repair pathway in glioblastoma cell lines.
Genes Cancer
PUBLISHED: 04-07-2014
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Temozolomide resistance is associated with multiple DNA repair pathways. We investigated homeobox (HOX) genes for their role in temozolomide resistance, focusing on the homologous recombination (HR) pathway, and we tested their therapeutic implications in conjunction with O(6)-methylguanine DNA methyltransferase (MGMT) status. Two glioblastoma cell lines with different MGMT statuses were used to test the augmented anticancer effect of temozolomide with HOXA10 inhibition. In vitro experiments, including gene expression studies with RNA interference, were performed to verify the related pathway dynamics. HOXA10 inhibition reinforced temozolomide sensitivity independent of MGMT status and was related to the impaired double-strand DNA breakage repair process resulting from the downregulation of Rad51 paralogs. Early growth response 1 (EGR1) and phosphatase and tensin homolog (PTEN) were the regulatory mediators between HOXA10 and the HR pathway. Moreover, HOXA10 inhibition selectively affected the nuclear function of PTEN without interfering with its cytoplasmic function of suppressing the phosphoinositide 3-kinase/Akt pathway. The mechanism of HR pathway regulation by HOXA10 harbors another target mechanism for overcoming temozolomide resistance in glioblastoma patients.
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Extended endoscopic endonasal approach for recurrent or residual adult craniopharyngiomas.
Acta Neurochir (Wien)
PUBLISHED: 04-02-2014
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The aim of this study was to evaluate the effectiveness of the extended endoscopic endonasal transsphenoidal approach (TSA) for recurrent or residual craniopharyngiomas, focusing on the extent of tumor resection and complications resulting from surgery at a single institution.
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Salvage Radiation Therapy for Isolated Local Recurrence of Extrahepatic Cholangiocarcinoma After Radical Surgery: A Retrospective Study.
Ann. Surg. Oncol.
PUBLISHED: 03-24-2014
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This study investigated the outcomes of salvage radiation therapy (RT) for isolated local recurrence of extrahepatic cholangiocarcinoma (EHCC) after radical surgery.
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The impact of no-reflow phenomena after primary percutaneous coronary intervention: a time-dependent analysis of mortality.
Coron. Artery Dis.
PUBLISHED: 03-15-2014
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The no-reflow phenomenon is a potential complication of primary percutaneous coronary intervention (PCI). Predictors of the no-reflow phenomenon and the impact on long-term mortality remain unclear.
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Transcatheter arterial chemoembolization and radiation therapy for treatment-naïve patients with locally advanced hepatocellular carcinoma.
Radiat Oncol J
PUBLISHED: 03-06-2014
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To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naïve patients with locally advanced hepatocellular carcinoma (HCC).
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Analysis of the BRAF(V600E) Mutation in Central Nervous System Tumors.
Transl Oncol
PUBLISHED: 03-05-2014
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BRAF(V600E) mutations are involved in the development of melanoma, colon cancer, and papillary thyroid carcinoma. These mutations are also found in primary brain tumors at low to moderate frequencies. In this study, we investigated a series of brain tumors to determine the prevalence and associated clinicopathologic features of BRAF(V600E) mutations. By direct sequencing, we analyzed 223 brain tumors, including 51 gangliogliomas (GGs), 45 pilocytic astrocytomas (PAs), 12 pleomorphic xanthoastrocytomas (PXAs), 35 glioblastomas (GBs), 28 anaplastic astrocytomas (AAs), 44 oligodendroglial tumors (ODGs), 3 anaplastic oligoastrocytomas, and 5 diffuse astrocytomas. Thirty-six cases (16.1%) exhibited the BRAF(V600E) mutation, including 66.7% of PXAs, 23.5% of GGs, 15.6% of PAs, and 9.7% of the malignant gliomas; the latter included 14.3% of AAs, 8.6% of GBs, and 4.5% of ODGs. Copy number aberration at the 7q34 (BRAF) locus was found in 73.1% of PAs and 50% of PXAs. 9p Homozygous deletion was found in 66.7% of PXAs, but it was not correlated with the BRAF(V600E) mutation. Patients' age, sex, histologic grade, and progression-free survival were also not correlated with the BRAF(V600E) mutation. The BRAF(V600E) mutation in brain tumors did not have prognostic value but is certainly a diagnostic marker and therapeutic target, not only for pediatric low-grade gliomas but also for malignant gliomas, even though the rate of mutation was not high. These results should be verified in a larger study with more cases and a longer follow-up period to overcome the limitation of small sample size.
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Added value of diffusion-weighted MRI for evaluating viable tumor of hepatocellular carcinomas treated with radiotherapy in patients with chronic liver disease.
AJR Am J Roentgenol
PUBLISHED: 02-27-2014
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The purpose of this article is to evaluate the added value of diffusion-weighted imaging (DWI) to the diagnostic performance of conventional MRI in diagnosing viable hepatocellular carcinoma (HCC) tumors treated with radiotherapy in patients with chronic liver disease.
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Evaluation of the microenvironmental heterogeneity in high-grade gliomas with IDH1/2 gene mutation using histogram analysis of diffusion-weighted imaging and dynamic-susceptibility contrast perfusion imaging.
J. Neurooncol.
PUBLISHED: 02-11-2014
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The purpose of our study was to explore the difference between isocitrate dehydrogenase (IDH)-1/2 gene mutation-positive and -negative high-grade gliomas (HGGs) using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. We enrolled 52 patients with histopathologically confirmed HGGs with IDH1/2 (P) (n = 16) or IDH1/2 (N) (n = 36). Histogram parameters of ADC and nCBV maps were correlated with gene mutations by using the unpaired student's t test and multivariable stepwise logistic regression analysis. The mean ADC value was higher in the IDH1 (P) group than IDH1 (N) (1,282.8 vs. 1,159.6 mm(2)/s, P = .0113). In terms of the cumulative ADC histograms, the 10th and 50th percentile values were also higher in the IDH1 (P) than IDH1 (N) (P = .0104 and .0183, respectively). We observed a higher 90th percentile value (3.121 vs. 2.397, P = .0208) and a steeper slope between the 10th (C10) and 90th (C90) of cumulative nCBV histograms (0.03386 vs. 0.02425/%, P = .0067) in the IDH1 (N) group. Multivariate analysis showed that the mean ADC mean value (P = .0048), the C90 value (P = .0113), and the slope between C10 and C90 (P = .0049) were the significant variables in the differentiation of IDH1 (P) from IDH1 (N). In conclusion, histogram analysis of ADC and nCBV maps based on entire tumor volume can be a useful tool for distinguishing IDH1 (P) and IDH1 (N), and it predicts that IDH (P) tumors have a more heterogeneous microenvironment than IDH (N) ones.
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Dosimetric effects of multileaf collimator leaf width on intensity-modulated radiotherapy for head and neck cancer.
Med Phys
PUBLISHED: 02-11-2014
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The authors evaluated the effects of multileaf collimator (MLC) leaf width (2.5 vs. 5 mm) on dosimetric parameters and delivery efficiencies of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) for head and neck (H&N) cancers.
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The role of diffusion-weighted magnetic resonance imaging in the treatment response evaluation of hepatocellular carcinoma patients treated with radiation therapy.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-09-2014
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We investigated the role of diffusion-weighted magnetic resonance imaging (DW MRI) as a response evaluation indicator for hepatocellular carcinoma (HCC) treated with radiation therapy (RT).
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Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction.
Cardiovasc Ultrasound
PUBLISHED: 02-06-2014
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We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI).
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The etiology of pectus carinatum involves overgrowth of costal cartilage and undergrowth of ribs.
J. Pediatr. Surg.
PUBLISHED: 01-31-2014
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We compared the length of costal cartilage and rib between patients with symmetric pectus carinatum and controls without anterior chest wall protrusion, using a 3-dimensional (3D) computed tomography (CT) to evaluate whether the overgrowth of costal cartilage exists in patients with pectus carinatum.
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Primary diffuse leptomeningeal glioneuronal tumors.
Brain Tumor Pathol
PUBLISHED: 01-29-2014
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Diffuse leptomeningeal disseminated glioneuronal tumor (DL-GNT) is a rare brain tumor that presents as a plaque-like subarachnoid tumor, commonly involving the basal cisterns and interhemispheric fissure of children but lacking intraparenchymal tumor. Histologically, the tumors are composed of sheets of monotonous rounded cells. Here, we report three cases of DL-GNTs, focusing on clinicopathologic features. Two patients were adult male, but one patient was child. The patients presented with seizures (n = 1) or headaches (n = 2). In all patients, radiography revealed characteristic leptomeningeal thickening and enhancement with minor superficial parenchymal lesions. All three cases were diffusely positive for both GFAP and synaptophysin, and scattered positive for OLIG2 and NeuN, but negative for IDH-1 (H09). Electron microscopic examination showed astrocytic and neuronal differentiation. The patient with the anaplastic tumor died due to aggressive progression of the tumor, but the remaining two patients were stable without tumor recurrence for 23 and 37 months. Thus, these findings suggest that DL-GNT can occur in both children and adult and both supra- and infra-tentorial leptomeninges. It has unique radiological and histopathological features and biological behavior. Further clinicopathological data with molecular genetic study are required for establishing DL-GNT as a unique entity.
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Rhabdoid glioblastoma is distinguishable from classical glioblastoma by cytogenetics and molecular genetics.
Hum. Pathol.
PUBLISHED: 01-25-2014
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The clinicopathologic and molecular genetic features of 5 cases of rhabdoid glioblastoma, an extremely rare variant of glioblastoma that tends to affect patients at a young age, were investigated by immunohistochemical analysis and focused molecular genetic studies including array-based comparative genomic hybridization. All 5 cases had supratentorial tumors that immunohistochemical analysis revealed to be robustly positive for epithelial membrane antigen, vimentin, p53, and PDGFR? (platelet-derived growth factor receptor, alpha polypeptide) but only focally positive for glial fibrillary acidic protein. Although complete retention of SMARCB1 (INI1) was observed in all 5 cases, epidermal growth factor receptor (EGFR) amplification, PTEN (phosphatase and tensin homolog) loss, homozygous deletion of cyclin-dependent kinase inhibitor 2A, 1p/19q codeletion, and isocitrate dehydrogenase 1 R132/IDH2 R172 mutation were not observed in any case, although a high level of EGFR polysomy was detected in 1 recurrent tumor. Although c-MET (MET protein) expression was focal but robustly positive in 3 cases, met proto-oncogene (MET) fluorescence in situ hybridization revealed low polysomy but not MET amplification. MGMT (O-6-methylguanine-DNA methyl-40 transferase) methylation-specific polymerase chain reaction revealed MGMT methylation in only 1 case. Furthermore, array-based comparative genomic hybridization revealed gain of chromosome 7 and loss of 1p, 6, 8p, 11, 13q, and 18q but no deletion of chromosome 22. In contrast to the classical subtype of primary glioblastoma, the cases studied here were characterized by the absence of EGFR amplification, PTEN loss, and 9p homozygous deletion and overexpression of p53, PDGFR?, and c-MET, suggesting that they can be classified as the proneural or mesenchymal subtype of glioblastoma and benefit from intensive therapy that includes temozolomide.
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Intraoperative predictors of early tracheal extubation after living-donor liver transplantation.
Korean J Anesthesiol
PUBLISHED: 01-19-2014
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Prolonged mechanical ventilation after liver transplantation has been associated with deleterious clinical outcomes, so early tracheal extubation posttransplant is now increasing. However, there is no universal clinical criterion for predicting early extubation in living-donor liver transplantation (LDLT). We investigated specific predictors of early extubation after LDLT.
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Effects of palmitoylation on the diffusional movement of BKCa channels in live cells.
FEBS Lett.
PUBLISHED: 01-08-2014
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BKCa channels are palmitoylated at a cluster of cysteine residues within the cytosolic linker connecting the 1st and 2nd transmembrane domains, and this lipid modification affects their surface expression. To verify the effects of palmitoylation on the diffusional dynamics of BKCa channels, we investigated their lateral movement. Compared to wild-type channels, the movement of mutant palmitoylation-deficient channels was much less confined and close to random. The diffusion of the mutant channel was also much faster than that of the wild type. Thus, the lateral movement of BKCa channels is greatly influenced by palmitoylation.
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An NMR metabolomics approach for the diagnosis of leptomeningeal carcinomatosis in lung adenocarcinoma cancer patients.
Int. J. Cancer
PUBLISHED: 01-07-2014
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Leptomeningeal carcinomatosis (LC) is a metastatic cancer invading the central nervous system (CNS). We previously reported a metabolomic diagnostic approach as tested on an animal model and compared with current modalities. Here, we provide a proof of concept by applying it to human LC originating from lung cancer, the most common cause of CNS metastasis. Cerebrospinal fluid from LC (n?=?26) and normal groups (n?=?41) were obtained, and the diagnosis was established with clinical signs, cytology, MRI and biochemical tests. The cytology on the CSF, the current gold standard, exhibited 69% sensitivity (?100% specificity) from the first round of CSF tapping. In comparison, the nuclear magnetic resonance spectra on the CSF showed a clear difference in the metabolic profile between the LC and normal groups. Multivariate analysis and cross-validation yielded the diagnostic sensitivity of 92%, the specificity of 96% and the area under the curve (AUC) of 0.991. Further spectral and statistical analysis identified myo-inositol (p?
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Two-week course of preoperative chemoradiotherapy followed by delayed surgery for rectal cancer: a phase II multi-institutional clinical trial (KROG 11-02).
Radiother Oncol
PUBLISHED: 01-07-2014
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The aim of this study was to evaluate the efficacy and safety of a two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer.
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Benefit of ?-blocker treatment for patients with acute myocardial infarction and preserved systolic function after percutaneous coronary intervention.
Heart
PUBLISHED: 01-06-2014
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?-blockers are the standard treatment for myocardial infarction (MI) based on evidence from the pre-thrombolytic era. The aim of this study was to examine the effect of ?-blocker treatment in patients with acute MI and preserved systolic function in the era of percutaneous coronary intervention (PCI).
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Effects of thymosin ?4 on wound healing of rat palatal mucosa.
Int. J. Mol. Med.
PUBLISHED: 01-02-2014
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The objective of the present study was to investigate the effect of thymosin ?4 (T?4) on the wound healing of rat palatal (RP) mucosa and related cellular properties. Cell viability, adhesion and migration of primary cultured RP cells were observed in the presence of T?4 at various concentrations ranging from 1 to 1,000 ng/ml. The mRNA and protein expression of matrix metalloproteinase 2 (MMP2) and vascular endothelial growth factor (VEGF) in T?4-treated RP cells was assessed by quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. For the in vivo assay, T?4 was applied to excisional wounds (3 mm in diameter) that were made in the center of the palate (n=6). Images of the wound areas were captured and assessed histologically one week after surgery. T?4 did not affect cell viability and adhesion, but RP cell migration was stimulated by T?4 at concentrations of 100 and 1,000 ng/ml. T?4 also increased the mRNA and protein expression of MMP2 and VEGF in RP cells. In the animal model, palatal wound closure was significantly enhanced in rats treated with T?4. The results of the present study indicated that T?4 promotes the wound healing of RP mucosa. Enhancement of RP cell migration and angiogenesis is likely to be involved in the promotion of wound healing.
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Hypofractionated chemoradiotherapy with temozolomide as a treatment option for glioblastoma patients with poor prognostic features.
Int. J. Clin. Oncol.
PUBLISHED: 01-01-2014
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Although the optimal treatment of frail glioblastoma patients is still controversial, previous randomized trials have excluded such patients. This study aimed to evaluate the feasibility and safety of hypofractionated radiotherapy (RT) with concomitant temozolomide for glioblastoma patients with poor prognostic features.
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A Highly Facile and Specific Assay for Cancer-Causing Isocitrate Dehydrogenase Mutant Using (13)C4-Labeled ?-Ketoglutarate and Heteronuclear NMR.
Anal. Chem.
PUBLISHED: 11-22-2013
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Isocitrate dehydrogenase mutations with neomorphic activity of converting ?-ketoglutarate to 2-hydroxyglutarate have been found in many types of cancers. We report an NMR-based assay specific for the mutant using (13)C4-labeled ?-ketoglutarate. It can be done in a complex mixture without extraction, give time-dependent absolute quantitation, and be applied to enzyme inhibition studies. Its merits over conventional assays should facilitate inhibitor developments for a new class of target-oriented anticancer agents.
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Factors associated with lateral pelvic recurrence after curative resection following neoadjuvant chemoradiotherapy in rectal cancer patients.
Int J Colorectal Dis
PUBLISHED: 11-17-2013
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This study aims to determine the risk factors for lateral pelvic recurrence (LPR) in rectal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and curative surgery.
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Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Radiation Therapy and Concomitant Temozolomide: Comparison Study of Standard and High-b-Value Diffusion-weighted Imaging.
Radiology
PUBLISHED: 10-28-2013
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Purpose To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm(2), respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide. Materials and Methods This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm(2), and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated. Results In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm(2) (ADC1000) and the ADC at b value of 3000 sec/mm(2) (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively. Conclusion The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. © RSNA, 2013 Online supplemental material is available for this article.
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Double suicide gene therapy using human neural stem cells against glioblastoma: double safety measures.
J. Neurooncol.
PUBLISHED: 09-22-2013
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With recent advancements in stem cell-based gene therapy, concerns about safety have grown. Stem cell-based gene therapies may pose the risk of immunological problems and oncogenesis. We investigated the feasibility of treating glioblastomas with neural stem cells [(NSCs), HB1.F3 cells] expressing double prodrug enzymes [cytosine deaminase (CD) and tyrosine kinase (TK)] to eliminate the NSCs following treatment for safety purposes. First, the in vitro and in vivo therapeutic efficacies of NSCs engineered with double prodrug enzymes (HB1.F3-CD.TK cells) were compared to cells expressing a single prodrug enzyme (HB1.F3-CD). Second, the degree of safety achieved by NSC elimination was compared with an in vitro viability assay of the NSCs after treatment with the double prodrugs. We further compared the differences in in vivo proliferation of control, single prodrug enzyme and double prodrug enzyme expressing NSCs. HB1.F3-CD.TK cells showed a better or comparable treatment outcome than HB1.F3-CD cells in vitro and in vivo. For safety, HB1.F3-CD.TK cells showed the least viability in vitro after treatment with prodrugs compared to HB1.F3 and HB1.F3-CD cells. Additionally, the in vivo proliferation among the injected NSCs found in the tumor was the smallest for HB1.F3-CD.TK cells. Double-prodrug enzyme-directed gene therapy shows good therapeutic efficacy as well as efficient eradication of the NSCs to ensure safety for clinical applications of stem cell-based gene therapies.
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Expression of miRNAs and ZEB1 and ZEB2 correlates with histopathological grade in papillary urothelial tumors of the urinary bladder.
Virchows Arch.
PUBLISHED: 09-10-2013
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Histopathological grading of papillary urothelial tumors (PUTs) of the urinary bladder is subjective and poorly reproducible. We investigated the relationship between the expression of frequently deregulated microRNAs (miRNAs) as well as their target genes (ZEB1/ZEB2) and bladder cancer histopathological grade in an attempt to find a miRNA that might allow more reliable grading of PUTs. We measured the expression levels of four miRNAs (miR-145, miR-205, miR-125b, and miR-200c) in 120 formalin-fixed, paraffin-embedded bladder tumor tissue samples using real-time PCR assays. ZEB1 and ZEB2 expression was assessed in the same bladder tissues by immunohistochemistry. MiR-205 distinguished low-grade papillary urothelial carcinoma (LG) from high-grade papillary urothelial carcinoma (HG), and miR-145 distinguished HG from infiltrating carcinoma (CA) with an area under the receiver operator characteristic curve (AUC) of 0.992 and 0.997, respectively (sensitivity/specificity of 95.8/96.7 % and 100/91.7 %, respectively; p?
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Design and synthesis of potent and selective P2X3 receptor antagonists derived from PPADS as potential pain modulators.
Eur J Med Chem
PUBLISHED: 08-16-2013
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Pyridoxalphosphate-6-azophenyl-2,4-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X3 receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS including phosphate and sulfonate groups were changed to carboxylic acids or deleted. The unstable azo (-NN-) linkage of 7a was transformed to more stable carbon-carbon, ether or amide linkages through the synthesis of the 5-hydroxyl-pyridine moieties with substituents at 2 position via a Diels-Alder reaction. This resulted in the retention of antagonistic activity (IC50 = 400 ? 700 nM) at the hP2X3 receptor in the two-electrode voltage clamp (TEVC) assay system on the Xenopus oocytes. Introduction of bulky aromatic groups at the carbon linker, as in compounds 13h-n, dramatically improved the selectivity profiles of hP2X3 when compared with mP2X1 and hP2X7 receptors. Among the substituents tested at the 2-position, the m-phenoxybenzyl group showed optimum selectivity and potency at the hP2X3 receptor. In searching for effective substituents at the 4- and 3-positions, we found that compound 36j, with 4-carboxaldehyde, 3-propenoic acid and 2-(m-phenoxy)benzyl groups, was the most potent and selective hP2X3 receptor antagonist with an IC50 of 60 nM at hP2X3 and marginal antagonistic activities of 10 ?M at mP2X1 and hP2X7. Furthermore, using an ex-vivo assay system, we found that compound 36j potently inhibited pain signaling in the rat dorsal horn with 20 ?M 36j displaying 65% inhibition while 20 ?M pregabalin, a clinically available drug, showed only 31% inhibition.
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Sorafenib-triggered radiation recall dermatitis with a disseminated exanthematous reaction.
Radiat Oncol J
PUBLISHED: 08-13-2013
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Sorafenib is a multi-targeted kinase inhibitor, which is the current standard treatment for advanced hepatocellular carcinoma (HCC). Only one case of radiation recall dermatitis (RRD) associated with sorafenib has been reported so far. Our patient with recurrent HCC was treated with palliative radiotherapy (RT) for the chest wall mass. Sorafenib at 400 mg twice daily was begun on the day following RT. On the 14th day post-RT, an erythematous patch was observed on right chest wall which matched area previously irradiated. It was consistent with RRD. Ten days later, a disseminated exanthematous rash and severe pruritus occurred. Sorafenib was stopped and an oral antihistamine was prescribed to relieve symptoms. At the 1-week follow-up after the cessation of sorafenib, all symptoms were resolved. Physicians should be alert to this recall phenomenon as it can occur both in the skin and elsewhere and the occurrence of RRD may be unpredictable.
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Impact of the Stent Length on Long-Term Clinical Outcomes Following Newer-Generation Drug-Eluting Stent Implantation.
Am. J. Cardiol.
PUBLISHED: 08-12-2013
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Stent length has been considered an important predictor of adverse events after percutaneous coronary intervention, even with the first-generation drug-eluting stents (DESs). The introduction of newer-generation DES has further reduced the rates of adverse clinical events such as restenosis, myocardial infarction, and stent thrombosis. The aim of this study was to compare the impact of stent length on the long-term clinical outcomes between first- and newer-generation DESs. The effects of stent length (?32 vs <32 mm) on the clinical outcomes were evaluated in 8,445 patients who underwent percutaneous coronary intervention using either a first-generation DES (sirolimus- and paclitaxel-eluting stents, n = 6,334) or a newer-generation DES (everolimus- and zotarolimus-eluting stents, n = 2,111) from January 2004 to December 2009. The 3-year adverse outcomes (composite of all-cause death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis) were compared using the inverse probability of treatment-weighted method according to the stent length. After adjustment for differences in the baseline risk factors, a stent length of ?32 mm was significantly associated with higher cumulative rates of target vessel revascularization and stent thrombosis in the patients treated with a first-generation DES (adjusted hazard ratio 1.875, 95% confidence interval 1.531 to 2.297, p <0.001; adjusted hazard ratio 2.964, 95% confidence interval 1.270 to 6.917, p = 0.012), but it was not associated with the clinical outcomes in patients treated with a newer-generation DES. In conclusion, stent length might not be associated with long-term clinical outcomes in newer-generation DES era, whereas stent length might be associated with long-term clinical outcomes in the first-generation DESs.
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Central neurocytoma: long-term outcomes of multimodal treatments and management strategies based on 30 years experience in a single institute.
Neurosurgery
PUBLISHED: 08-03-2013
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A thorough investigation of the long-term outcomes of central neurocytoma (CN) after different treatments is required to establish optimal management strategies.
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Agronomic and genetic analysis of Suweon 542, a rice floury mutant line suitable for dry milling.
Rice (N Y)
PUBLISHED: 07-25-2013
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Producing rice flour of good quality by dry milling is necessary to reduce milling costs and promote the processed rice food industry. This study was conducted to evaluate the dry milling properties of Suweon 542, a floury endosperm mutant, and identify the chromosomal region responsible for the floury endosperm characteristics.
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Does overgrowth of costal cartilage cause pectus carinatum? A three-dimensional computed tomography evaluation of rib length and costal cartilage length in patients with asymmetric pectus carinatum.
Interact Cardiovasc Thorac Surg
PUBLISHED: 07-17-2013
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To evaluate whether the overgrowth of costal cartilage may cause pectus carinatum using three-dimensional (3D) computed tomography (CT).
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Effects of magnesium pretreatment on the levels of T helper cytokines and on the severity of reperfusion syndrome in patients undergoing living donor liver transplantation.
Magnes Res
PUBLISHED: 07-03-2013
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Magnesium has protective effects in ischaemia-reperfusion injury, and is involved in immunomodulation. We investigated the effects of magnesium pretreatment on the secretion of T helper (Th) cytokines and on the severity of post-reperfusion syndrome (PRS) in patients undergoing living donor liver transplantation (LDLT).
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A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma.
Neuro-oncology
PUBLISHED: 06-25-2013
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To determine the benefit of surgical management in recurrent glioblastoma, we analyzed a series of patients with recurrent glioblastoma who had undergone surgery, and we devised a new scale to predict their survival.
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Diagnosis of acute global myocarditis using cardiac MRI with quantitative t1 and t2 mapping: case report and literature review.
Korean J Radiol
PUBLISHED: 06-20-2013
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The diagnosis of myocarditis can be challenging given that symptoms, clinical exam findings, electrocardiogram results, biomarkers, and echocardiogram results are often non-specific. Endocardial biopsy is an established method for diagnosing myocarditis, but carries the risk of complications and false negative results. Cardiac magnetic resonance imaging (MRI) has become the primary non-invasive imaging tool in patients with suspected myocarditis. Myocarditis can be diagnosed by using three tissue markers including edema, hyperemia/capillary leak, and necrosis/fibrosis. The interpretation of cardiac MR findings can be confusing, especially when the myocardium is diffusely involved. Using T1 and T2 maps, the diagnosis of myocarditis can be made even in cases of global myocarditis with the help of quantitative analysis. We herein describe a case of acute global myocarditis which was diagnosed by using quantitative T1 and T2 mapping.
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Predictive factors for Child-Pugh score elevation in hepatocellular carcinoma patients treated with conformal radiation therapy: dose-volume histogram analysis.
Tumori
PUBLISHED: 06-11-2013
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We designed the study to identify the clinical and dose-volumetric parameters associated with the risk of Child-Pugh score elevation in hepatocellular carcinoma patients treated with conformal radiation therapy.
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Quantitative T2 mapping for detecting myocardial edema after reperfusion of myocardial infarction: validation and comparison with T2-weighted images.
Int J Cardiovasc Imaging
PUBLISHED: 04-14-2013
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This study evaluates the clinical usefulness of T2 mapping for the detection of myocardial edema in the re-perfused acute myocardial infarction (MI). Cardiac MRIs were reviewed in 20 patients who had acute MI after reperfusion therapy. The regional T2 values and T2-weighted image (T2WI) signal intensities (SI) were measured in the infarcted and remote zones of the myocardium. Patients were divided into three groups according to the signal patterns of the infarcted myocardium on the T2WIs. The T2 values of the infarcted zones were compared on the T2 maps among the three groups. Validation of the T2 values was performed in the normal myocardium of seven healthy volunteers. There were no significant differences in mean T2WI-SI or T2 values in the normal myocardium of healthy volunteers compared to the remote myocardium of acute MI patients (p > 0.05). Mean SI on the T2WIs was significantly higher in the infarcted myocardium (81.3 ± 37.6) than in the remote myocardium (63.8 ± 18.1) (p < 0.05). The T2WIs showed high SI in ten patients (group 1), iso-SI in seven (group 2), and low SI in three (group 3) in the infarcted myocardium, compared to the remote myocardium. The T2 maps showed that T2 values in the infarcted myocardium had mostly increased, regardless of group, with values of 71 ± 9 ms in group 1, 64.9 ± 7.4 ms in group 2, and 61.4 ± 8.5 ms in group 3. T2 mapping is superior to T2WI for detecting areas of high SI in the infarcted myocardium. Therefore, quantitative T2 mapping sequences may be more useful and reliable in identifying myocardial edema in the infarcted myocardium than T2WI.
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True progression versus pseudoprogression in the treatment of glioblastomas: a comparison study of normalized cerebral blood volume and apparent diffusion coefficient by histogram analysis.
Korean J Radiol
PUBLISHED: 04-04-2013
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The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps.
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Radiosurgery for central neurocytoma: long-term outcome and failure pattern.
J. Neurooncol.
PUBLISHED: 03-10-2013
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Despite the favorable outcomes of radiosurgery for central neurocytoma (CN), these results are based on case series that included a limited number of patients and short follow-up periods because of the scarcity of CN. Because CN is a benign tumor with an indolent clinical course, long-term follow-up and analysis of failure pattern are required for the establishment of the role of radiosurgery in the management of CN. Twenty consecutive patients (10 patients who received Gamma Knife radiosurgery (GKRS) as a primary treatment and 10 patients who received GKRS as a secondary treatment) with a radiological follow-up period ?36 months were included in this study. The mean radiological follow-up duration was 100 months (range 43-149 months). The mean tumor volume was 10.4 cm(3) (range 0.4-36.4 cm(3)) and the mean marginal dose was 15.4 Gy (range 9-20 Gy). Local control failure was found in six patients at the last radiological follow-up. Overall actuarial local control rates were 89.5 % at 5 years and 83.1 % at 10 years. The primary GKRS group included two cases with local failure, with cyst formation or local recurrence. In contrast, in the secondary GKRS group, local control failure was found in four cases (including three cases with an "out-of-field recurrence" pattern) and occurred earlier compared with the primary GKRS group. Our study suggests that GKRS could be a primary or secondary treatment option for CN. However, long-term radiological follow-up is mandatory. In particular, more careful consideration during margin delineation and planning procedure is required in the secondary GKRS group.
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Stereotactic radiosurgery for brain metastases from hepatocellular carcinoma.
J. Neurooncol.
PUBLISHED: 03-08-2013
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The purpose of this study is to investigate the possible role of stereotactic radiosurgery (SRS) in the management of patients with brain metastases from hepatocellular carcinoma (HCC). Thirty-two consecutive patients with 80 brain metastases from HCC were treated with SRS. Twenty-eight (87.5 %) patients were male, and the mean age of the patients was 54 ± 12 years (range 22-73). Twenty-seven (84.4 %) patients were classified as RTOG RPA Class 2. The mean tumor volume was 6.14 ± 11.3 cm(3) (range 0.01-67.3). The mean marginal dose prescribed was 20.1 ± 3.6 Gy (range 10.0-25.0). The median overall survival time after SRS was 11.3 ± 5.8 weeks (95 % CI 0-22.7). A greater total volume of brain metastases (>14 cm(3)) was the only independent prognostic factor (HR = 2.419; 95 % CI 1.040-5.624; p = 0.040). The actuarial control rate of brain metastases was 51.3 % at 4 months after SRS. The prescribed marginal dose (>18 Gy) was significantly related with the actuarial tumor control (HR = 0.254; 95 % CI 0.089-0.725; p = 0.010). The prognosis of patients with brain metastases from HCC is dismal even with the modern technology of radiosurgery. The marginal dose prescribed should be reevaluated to improve upon the current poor local control rates.
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Enrichment of cancer cells from whole blood using a microfabricated porous filter.
Anal. Biochem.
PUBLISHED: 02-22-2013
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Enrichment of circulating tumor cells (CTCs) from whole blood is very challenging due to its rarity. We have developed a new CTC enrichment method using a microfabricated filter. The filter was designed to fractionate tumor cells by cell size and optimized to have high porosity and proper pore distribution. When cancer cells were spiked in whole blood, the average recovery rate was 82.0 to 86.7% and the limit of detection by filtration process was approximately 2 cancer cells in a testing volume of blood. The results indicate that the microfabricated filter-based enrichment would be useful to retrieve and analyze CTCs in practice.
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Seizures during the management of high-grade gliomas: clinical relevance to disease progression.
J. Neurooncol.
PUBLISHED: 02-20-2013
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This study was performed to evaluate the incidence of seizures with its implications on disease progression and the diagnostic value of post-ictal magnetic resonance images (MRI) during the management of high-grade gliomas (HGGs). A total of 406 consecutive patients with newly diagnosed HGGs were retrospectively reviewed. The incidence of seizures during the management was investigated. In patients who experienced a seizure, the causality between seizures and disease progression was assessed by pre-ictal, post-ictal (<1 month), and follow-up (<3 months) MRI. After a median follow-up of 17.4 months (range 0.1-88.3), seizures developed in 127 patients (31 %). Of the 127 patients, radiological progression at the post-ictal MRI was found in 83 patients (65 %) and the follow-up MRI confirmed progression in 79 patients (62 %). Four other patients (3 %) were shown to be progression-free. Among those without radiological progression at the post-ictal MRI, the follow-up MRI confirmed progression-free in 31 patients (24 %); however, 13 patients (10 %) revealed eventual progression. In the patients with a seizure, absence of preoperative seizures (p = 0.003), <95 % tumor resection (p = 0.001), and pre-ictal Karnofsky Performance Scale score ? 70 (p = 0.025) were significantly associated with disease progression. During the management of HGG, 31 % of patients experienced seizures; of these patients, 72 % harbored progressive disease. The post-ictal MRI is useful for detecting disease progression; however, there are pitfalls. Clinical settings should be considered together for diagnosing disease progression in patients with seizures.
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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.