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Find video protocols related to scientific articles indexed in Pubmed.
Hierarchical superstructures from a star-shaped molecule consisting of a cyclic oligosiloxane with cyanobiphenyl moieties.
Soft Matter
PUBLISHED: 11-20-2014
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Unconventional star-shaped liquid crystals (abbreviated as SiLCs) were successfully synthesized by chemically connecting four cyanobiphenyl anisotropic mesogens to the periphery of a super-hydrophobic and ultra-flexible cyclic tetramethyltetrasiloxane ring with flexible hexyl chains. Based on the combined experimental techniques of differential scanning calorimetry (DSC), cross-polarized optical microscopy (POM), solid-state carbon-13 ((13)C) nuclear magnetic resonance (NMR) spectroscopy and one-dimensional (1D) wide-angle X-ray diffraction (WAXD), it was found that the SiLC molecule exhibited the monotropic phase transition from a LC phase to a crystalline phase. The crystalline phase was only detected during slow heating processes above its glass transition temperature, while a LC phase was formed both during cooling and during heating processes. The hierarchical superstructures were identified from the structure-sensitive 2D WAXD of the macroscopically oriented SiLC film and confirmed by selected area electron diffraction (SAED) of the SiLC single crystals. The molecular packing symmetry in the monoclinic unit cell was further investigated by computer simulations on the real and reciprocal spaces. Macroscopically oriented SiLC hierarchical superstructures on the different length scales may provide the targeted physical properties, which can allow us to apply SiLC molecules in the fields of electro-optical devices and nonlinear optics.
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Detection of Occult Primary Tumors in Patients with Cervical Metastases of Unknown Primary Tumors: Comparison of (18)F FDG PET/CT with Contrast-enhanced CT or CT/MR Imaging-Prospective Study.
Radiology
PUBLISHED: 11-19-2014
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Purpose To assess diagnostic accuracy of fluorine 18 ((18)F) fluorodeoxyglucose ( FDG fluorodeoxyglucose ) combined positron emission tomography (PET) and computed tomography (CT) in the detection of occult primary tumors and determination of optimal care in patients with cervical metastasis of an unknown primary tumor ( CUP cervical lymph node metastasis from an unknown primary tumor ) compared with contrast material-enhanced CT alone or combined contrast-enhanced CT and magnetic resonance (MR) imaging (CT/MR imaging). Materials and Methods Institutional review board approval and written informed consent were obtained. In total, 56 patients with initially undetected tumors after endoscopic or physical examination were prospectively assessed with (18)F FDG fluorodeoxyglucose PET/CT and contrast-enhanced CT or contrast-enhanced CT/MR imaging. The contrast-enhanced CT/MR images were read in combination. Results of guided biopsy with general anesthesia served as the reference standard. Diagnostic values of (18)F FDG fluorodeoxyglucose PET/CT, contrast-enhanced CT, and contrast-enhanced CT/MR imaging were compared with the McNemar test. Results Primary tumors were detected at 32 sites in 31 (55%) of 56 patients. There were 26 tumors in the palatine tonsil, two in the hypopharynx, two in the base of the tongue, and two in the nasopharynx. PET/CT depicted 22 (69%) of 32 primary tumors, but it failed to depict primary tumors in 10 (31%) of 32 cases. Overall, sensitivity of PET/CT (69%) in detection of primary tumors was higher than that of contrast-enhanced CT (16%) (P < .001) or contrast-enhanced CT/MR imaging (41%) (P = .039), while specificity of these methods did not differ (88%, 76%, and 59% for PET/CT, contrast-enhanced CT, and contrast-enhanced CT/MR imaging, respectively; P > .4). Diagnostic performance (area under the receiver operating characteristics curve [ AUC area under the receiver operating characteristics curve ] = 0.759) of PET/CT in tumor detection was significantly better than that of contrast-enhanced CT alone ( AUC area under the receiver operating characteristics curve = 0.531) (P = .001) or contrast-enhanced CT/MR imaging ( AUC area under the receiver operating characteristics curve = 0.537) (P = .036). PET/CT depicted primary tumors in eight (50%) of 16 cases of false-negative CT/MR imaging findings, one distant metastatic case, and two cases of synchronous cancer. Conclusion (18)F FDG fluorodeoxyglucose PET/CT is more sensitive in detection of primary tumors than is contrast-enhanced CT or contrast-enhanced CT/MR imaging in patients with CUP cervical lymph node metastasis from an unknown primary tumor ; therefore, it may lead to improved therapeutic planning in these patients. © RSNA, 2014.
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Epithelial-Mesenchymal Transition: Clinical Implications for Nodal Metastasis and Prognosis of Tongue Cancer.
Otolaryngol Head Neck Surg
PUBLISHED: 11-13-2014
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The development of biomarkers for the prediction of lymph node metastasis and prognosis is critical for deciding the treatment modality of tongue cancer. The purpose of our study is to investigate the clinical implications of epithelial-mesenchymal transition (EMT) expression in tongue cancer.
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Clinical significance of intensive endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma.
Scand. J. Gastroenterol.
PUBLISHED: 11-06-2014
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Abstract Objectives. Patients with head and neck squamous cell carcinoma (HNSCC) often develop second primary tumors in the upper aerodigestive tract. Early detection of synchronous esophageal squamous cell neoplasm (ESCN) is important because the prognosis of HNSCC can be affected by the statuses of second primary tumors. Methods. In a prospective study, 308 patients with HNSCC were screened for synchronous ESCN between May 2010 and April 2012. All patients underwent conventional white-light endoscopic examination with Lugol chromoendoscopy and narrow band image. Results. The median age was 61 years (range, 26-87 years), and the male-to-female ratio was 4.2:1. Two hundred and thirty-four patients (76.0%) were current or ex-smokers, 207 patients (67.2%) had a history of alcohol consumption and 56 patients (18.2%) had previous history of cancer. Synchronous ESCN was detected in 22 patients (7.1%), and most patients were at an early stage. The locations of index HNSCC in these patients were as follows: hypopharynx (n = 12), larynx (n = 6), oropharynx (n = 2) and oral cavity (n = 2). Synchronous ESCN was detected in 25.5% (12/47) of hypopharyngeal cancer and in 27.8% (15/54) of HNSCC involving the pyriform sinus. Multivariate analysis showed that smoking (current smoker vs. never smoker, Odds Ratio [OR] 8.3, p = 0.028), a history of cancer (OR 5.0, p = 0.002) and pyriform sinus involvement (OR 9.2, p < 0.0001) increased the risk of developing synchronous ESCN. Conclusions. Patients with HNSCC, especially those who are current smokers, have a history of cancer and have pyriform sinus involvement, should undergo intensive endoscopic screening to detect synchronous ESCN.
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Prominent protein Z-induced thrombin inhibition in cirrhosis: A new functional assay for hypercoagulability assessment.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-29-2014
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Protein Z (PZ) is an anticoagulant that accelerates the inhibitory effect of PZ-dependent protease inhibitor (ZPI) on coagulation factor Xa. We assessed functional status of PZ system in 158 patients with liver cirrhosis and 59 healthy controls.
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Cell therapy with embryonic stem cell-derived cardiomyocytes encapsulated in injectable nanomatrix gel enhances cell engraftment and promotes cardiac repair.
ACS Nano
PUBLISHED: 09-15-2014
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A significant barrier to the therapeutic use of stem cells is poor cell retention in vivo. Here, we evaluate the therapeutic potential and long-term engraftment of cardiomyocytes (CMs) derived from mouse embryonic stem cells (mESCs) encapsulated in an injectable nanomatrix gel consisting of peptide amphiphiles incorporating cell adhesive ligand Arg-Gly-Asp-Ser (PA-RGDS) in experimental myocardial infarction (MI). We cultured rat neonatal CMs in PA-RGDS for 7 days and found that more than 90% of the CMs survived. Next, we intramyocardially injected mouse CM cell line HL-1 CMs with or without PA-RGDS into uninjured hearts. Histologic examination and flow cytometry analysis of digested heart tissues showed approximately 3-fold higher engraftment in the mice that received CMs with PA-RGDS compared to those without PA-RGDS. We further investigated the therapeutic effects and long-term engraftment of mESC-CMs with PA-RGDS on MI in comparison with PBS control, CM-only, and PA-RGDS only. Echocardiography demonstrated that the CM-only and CM+PA-RGDS groups showed higher cardiac function at week 2 compared to other groups. However, from 3 weeks, higher cardiac function was maintained only in the CM+PA-RGDS group; this was sustained for 12 weeks. Confocal microscopic examination of the cardiac tissues harvested at 14 weeks demonstrated sustained engraftment and integration of mESC-CMs into host myocardium in the CM+PA-RGDS group only. This study for the first time demonstrated that PA-RGDS encapsulation can enhance survival of mESC-derived CMs and improve cardiac function post-MI. This nanomatrix gel-mediated stem cell therapy can be a promising option for treating MI.
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Association between predonation serum uric acid concentration and change in renal function after living kidney donation in women.
Intern Med J
PUBLISHED: 09-14-2014
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Reduction in renal mass after unilateral nephrectomy causes functional and structural changes in the remaining kidney. We investigated the association between predonation serum uric acid (SUA) concentration and the change in renal function after living kidney donation.
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BCLC System Provides the Best Discrimination Ability for Survival of Untreated Hepatocellular Carcinoma Patients in an HBV-endemic Area.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-13-2014
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A uniform staging system for hepatocellular carcinoma (HCC) is needed. In this study, the discrimination abilities of HCC staging systems (AJCC, BCLC, CLIP and Okuda stage) were compared during the course of untreated HCC.
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CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis.
Liver Int.
PUBLISHED: 08-28-2014
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Accurate prognostication of acute-on-chronic liver failure (ACLF) is essential for therapeutic decisions. Our aim was to validate a novel scoring system for predicting mortality, the chronic liver failure-sequential organ failure assessment (CLIF-SOFA), in a population of Asian patients with ACLF.
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Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.
Antimicrob. Agents Chemother.
PUBLISHED: 08-25-2014
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The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.
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Does 18F-FDG positron emission tomography-computed tomography have a role in initial staging of hepatocellular carcinoma?
PLoS ONE
PUBLISHED: 08-25-2014
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The utility of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET/CT) in initial staging of hepatocellular carcinoma (HCC) has yet to be fully explored. We assessed the usefulness of (18)F-FDG PET/CT in initial staging of HCC.
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Cytoplasmic iASPP Expression as a Novel Prognostic Indicator in Oral Cavity Squamous Cell Carcinoma.
Ann. Surg. Oncol.
PUBLISHED: 08-23-2014
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Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a key inhibitor of tumor suppressor p53 that is overexpressed in several human cancers; however, its role in oral cavity squamous cell carcinomas (OSCC) remains unknown. The present study investigated the prognostic role of iASPP in patients with OSCC.
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Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.
Eur Arch Otorhinolaryngol
PUBLISHED: 08-23-2014
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Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72 %) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73 %) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80 %, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78 %. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP.
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Effect of preemptive treatment with human umbilical cord blood-derived mesenchymal stem cells on the development of renal ischemia-reperfusion injury in mice.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 08-20-2014
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Human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) have been studied in several models of immune-mediated disease because of their unique immunomodulatory properties. We hypothesized that HUCB-MSCs could suppress the inflammatory response in postischemic kidneys and attenuate early renal injury. In 8- to 10-wk-old male C57BL/6 mice, bilateral ischemia-reperfusion injury (IRI) surgery was performed, and 1 × 10(6) HUCB-MSCs were injected intraperitoneally 24 h before surgery and during reperfusion. Renal functional and histological changes, HUCB-MSC trafficking, leukocyte infiltration, and cytokine expression were analyzed. Renal functional decline and tubular injury after IRI were attenuated by HUCB-MSC treatment. PKH-26-labeled HUCB-MSCs trafficked into the postischemic kidney. Although numbers of CD45-positive leukocytes in the postischemic kidney were comparable between groups, the expression of interferon-? in the postischemic kidney was suppressed by HUCB-MSC treatment. The rapid decrease in intrarenal VEGF after IRI was markedly mitigated by HUCB-MSC treatment. In inflammatory conditions simulated in a cell culture experiment, VEGF secretion from HUCB-MSCs was substantially enhanced. VEGF inhibitor abolished the renoprotective effect of HUCB-MSCs after IRI. Flow cytometry analysis revealed the decreased infiltration of natural killer T cells and increased number of regulatory T cells in postischemic kidneys. In addition, these effects of HUCB-MSCs on kidney infiltrating mononuclear cells after IRI were attenuated by VEGF inhibitor. HUCB-MSCs attenuated renal injury in mice in the early injury phase after IRI, mainly by humoral effects and secretion of VEGF. Our results suggest a promising role for HUCB-MSCs in the treatment of renal IRI.
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Tauroursodeoxycholic Acid, a Bile Acid, Promotes Blood Vessel Repair by Recruiting Vasculogenic Progenitor Cells.
Stem Cells
PUBLISHED: 07-29-2014
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Although serum bile acid concentrations are ~10 ?M in healthy subjects, the cross-talk between the biliary system and vascular repair has never been investigated. In this study, tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34(+) hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34(+) /Sca1(+) progenitors in mice peripheral blood (PB), and CD34(+) , CD31(+) , and c-kit(+) progenitors in human PB. In addition, TUDCA increased differentiation of CD34(+) HSCs into EPC lineage cells via Akt activation. EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein (FAP) via Akt activation. Interestingly, TUDCA induced integration of EPCs into human aortic endothelial cells (HAECs) by increasing adhesion molecule expression. In the mouse hindlimb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1(+) /CD34(+) and Sca-1(+) /c-kit(+) progenitors into damaged tissue. In GFP(+) bone marrow-transplanted hindlimb ischemia, TUDCA induced recruitment of GFP(+) /c-kit(+) progenitors to the ischemic area, resulting in an increased blood perfusion ratio. Histological analysis suggested that GFP(+) progenitors mobilized from bone marrow, integrated into blood vessels, and differentiated into VEGFR(+) cells. In addition, TUDCA decreased cellular senescence by reducing levels of p53, p21, and reactive oxygen species and increased nitric oxide. Transplantation of TUDCA-primed senescent EPCs in hindlimb ischemia significantly improved blood vessel regeneration, as compared with senescent EPCs. Our results suggested that TUDCA promoted neovascularization by enhancing the mobilization of stem/progenitor cells from bone marrow, their differentiation into EPCs, and their integration with preexisting endothelial cells. This article is protected by copyright. All rights reserved.
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Combinational chemoprevention effect of celecoxib and an oral antiangiogenic LHD4 on colorectal carcinogenesis in mice.
Anticancer Drugs
PUBLISHED: 07-09-2014
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To achieve a clinically rational regimen for cancer chemoprevention with improved efficacy and safety, the combination effect of celecoxib and newly developed oral angiogenesis inhibitor, LHD4, on chemoprevention was evaluated. The chemopreventive effects of celecoxib, LHD4, and the combination of celecoxib and LHD4 were evaluated in a murine colorectal carcinogenesis model. After 17 experimental weeks, mouse colon tissues were collected and examined in terms of polyp volume and degree of carcinogenesis, inflammation, and angiogenesis. Mice in the celecoxib-treated or LHD4-treated groups had total polyp volumes of 47.0±9.7 and 120.1±45.2?mm, respectively, which represented decreases of 65.6 and 22.3% from the control (154.5±33.5?mm). However, the polyp volume in the combination group was 22.8±9.3?mm, a decrease of 85.2% from the control. In the comparison of carcinogenesis, the percentage of normal tissue (i.e. excluding proliferative tissue) was found to be 40.6% in the control, 51.7% in the celecoxib, 56.9% in the LHD4, and 81.7% in the combination group. In accordance with attenuated carcinogenesis, both inflammation and angiogenesis were also well controlled. Together, these results suggest that the combinatory use of celecoxib and a newly developed oral heparin conjugate could be a promising regimen for chemoprevention by intervening in both inflammation and angiogenesis.
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Mdm2 and p53 Expression in Radiation-Induced Sarcomas of the Head and Neck: Comparison with De Novo Sarcomas.
Korean J Pathol
PUBLISHED: 06-30-2014
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The pathogenesis of radiation-induced sarcomas (RISs) is not well known. In RIS, TP53 mutations are frequent, but little is known about Mdm2-p53 interaction, which is a recent therapeutic target of sarcomas.
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A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase.
Korean J. Intern. Med.
PUBLISHED: 06-15-2014
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Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated.
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Late gadolinium enhancement magnetic resonance imaging for the assessment of myocardial infarction: comparison of image quality between single and double doses of contrast agents.
Int J Cardiovasc Imaging
PUBLISHED: 06-09-2014
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To compare the image quality of late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMR) using a single dose of gadolinium contrast agent versus the conventional double dose for assessing myocardial infarction. This retrospective study examined 37 patients with chronic myocardial infarction who underwent LGE CMR using both inversion recovery (IR)-turbo fast low-angle shot magnitude-reconstructed and phase-sensitive images with two different dosages of gadolinium contrast agent: a single dose of 0.1 mmol/kg gadolinium-DTPA in 17 patients and a double dose of 0.2 mmol/kg in 20 patients. The contrast-to-noise ratio (CNR) and visual conspicuity between infarct and normal myocardium (CNRinfarct-normal, conspicuityinfarct-normal) and between infarct and left ventricular cavity (CNRinfarct-LVC, conspicuityinfarct-LVC) were compared. Interobserver agreement for the maximal transmural extent of infarction was also evaluated. CNRinfarct-normal was significantly higher with double-dose gadolinium contrast agent (15.5 ± 20.7 vs. 40.4 ± 16.1 in magnitude images and 9.5 ± 2.8 vs. 11.2 ± 2.7 in phase-sensitive images, P < 0.001) while conspicuityinfarct-normal showed no significant difference between the two groups (P > 0.05). Both CNRinfarct-LVC (7.7 ± 10.7 vs. -6.6 ± 19.0 in magnitude images and 4.1 ± 2.3 vs. -0.4 ± 4.1 in phase-sensitive images, P < 0.05) and conspicuityinfarct-LVC were significantly better with single-dose gadolinium contrast. Interobserver agreement for assessing the transmural extent of infarction was moderate in both groups: 0.591 for single-dose and 0.472 for double-dose. LGE CMR using a single dose of gadolinium contrast agent showed significantly better contrast between infarcted myocardium and left ventricular cavity lumen without a significant decrease in visual contrast between infarcted myocardium and normal myocardium, compared to a double dose.
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Association of Polymorphism in MicroRNA 604 with Susceptibility to Persistent Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma.
J. Korean Med. Sci.
PUBLISHED: 05-19-2014
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MicroRNA polymorphisms may be associated with carcinogenesis or immunopathogenesis of infection. We evaluated whether the mircoRNA-604 (miR-604) polymorphism can affect the persistence of hepatitis B virus (HBV) infection, and the development to hepatocellular carcinoma (HCC) in patients with chronic HBV infection. A total of 1,439 subjects, who have either past or present HBV infection, were enrolled and divided into four groups (spontaneous recovery, chronic HBV carrier without cirrhosis, liver cirrhosis and HCC). We genotyped the precursor miR-604 genome region polymorphism. The CC genotype of miR-604 rs2368392 was most frequently observed and T allele frequency was 0.326 in all study subjects. The HBV persistence after infection was higher in those subjects with miR-604 T allele (P=0.05 in a co-dominant and dominant model), which implied that the patients with miR-604 T allele may have a higher risk for HBV chronicity. In contrast, there was a higher rate of the miR-604 T allele in the chronic carrier without HCC patients, compared to those of the HCC patients (P=0.03 in a co-dominant model, P=0.02 in a recessive model). The T allele at miR-604 rs2368392 may be a risk allele for the chronicity of HBV infection, but may be a protective allele for the progression to HCC in chronic HBV carriers.
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Clinical relevance of urinary angiotensinogen and renin as potential biomarkers in patients with overt proteinuria.
Transl Res
PUBLISHED: 05-18-2014
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Urinary angiotensinogen (AGT) and renin have been reported to reflect the intrarenal renin-angiotensin system (RAS) activity. However, the adequacy and clinical significance of these markers have not been evaluated in overtly proteinuric patients. In patients with biopsy-proven glomerulonephritis, plasma and urinary AGT and renin were analyzed. A cohort of 75 patients treated with RAS inhibitors was followed for 1 year. Among the 207 patients, 105 had subnephrotic and 102 had nephrotic-range proteinuria. Mean age, estimated glomerular filtration rate (eGFR), and urinary protein-to-creatinine ratio (P/Cr) of all patients were 48 years, 79.7 mL/min/1.73 m(2), and 5.66 mg/mg, respectively. Both natural logarithm of urinary AGT/creatinine (ln [urinary AGT/Cr]) and ln (urinary renin/Cr) showed positive correlations with urinary P/Cr. There was a positive correlation between ln (urinary AGT/Cr) and ln (urinary renin/Cr). Ln (urinary renin/Cr) was not affected by ln (plasma renin) regardless of the degree of proteinuria. The treatment response to RAS inhibitors was greatest in patients with high urinary AGT and renin. However, the predictive value of those parameters was no longer present when the values were adjusted by the degree of proteinuria. Ln (urinary renin/Cr) and initial eGFR were independently associated with the changes in renal function for 1 year. Ln (urinary AGT/Cr) was associated with persistent overt proteinuria after 1 year. Our study suggests that urinary renin may be a better marker in heavy proteinuria, and the treatment response to RAS inhibitors may be enhanced in patients with high urinary renin and AGT. Further studies will be necessary to explore the value of urinary AGT and renin.
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JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs.
Mol Med Rep
PUBLISHED: 05-15-2014
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Liver cancer is one of the most drug-resistant cancer types, and cancer stem cells are related to drug resistance. c-Jun-N-terminal kinase (JNK) signaling is involved in drug resistance, and the side population of cells (SP cells) can be used as a model to study liver cancer stem cells. We sought to evaluate the relationship between SP cells and JNK signaling in hepatocarcinoma cells. For this purpose, we examined cell proliferation and the SP cell ratio following treatment of Huh7 cells with the anticancer drugs 5-fluorouracil (5-FU) and paclitaxel. The expression of phospho-stress-activated protein kinase (SAPK)/JNK in the treated cells was evaluated using immunoblotting. 5-FU and paclitaxel treatment increased the number of SP cells and JNK phosphorylation, and decreased cell survival. Huh7 and HepG2 cells were also treated with SP600125, a JNK inhibitor, to study the relationship between SP cells and JNK signaling. The increase in the number of SP cells and the SAPK/JNK and c-Jun phosphorylation was reverted by SP600125 treatment in these cells. We also used immunohistochemistry and showed that SAPK/JNK and c-Jun phosphorylation are increased in hepatocarcinoma tissues. In conclusion, our results demonstrate that the number of SP cells and SAPK/JNK phosphorylation are increased upon treatment with anticancer drugs, and that this increase is blocked by inhibition of JNK signaling. These findings suggest that drug resistance in liver cancer may involve an increase in the number of SP cells following JNK activation.
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Clinical relevance of procalcitonin and C-reactive protein as infection markers in renal impairment: a cross sectional study.
Crit Care
PUBLISHED: 05-11-2014
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IntroductionAlthough the clinical application of procalcitonin (PCT) as an infection marker in patients with impaired renal function (estimated glomerular filtration rate (eGFR) <60 ml/min) has been increasing recently, it is unclear whether PCT is more accurate than C-reactive protein (CRP). We investigated the clinical value of CRP and PCT based on renal function.MethodsFrom November 2008 to July 2011, a total of 493 patients who simultaneously underwent CRP and PCT tests were enrolled. The area under the receiver operating characteristic (ROC) curve and characteristics of both markers were analyzed according to infection severity and renal function.ResultsIn patients with impaired renal function, the area under the ROC curve was 0.876 for CRP and 0.876 for PCT. In patients with infection, CRP levels differed depending on whether the infection was localized, septic, or severely septic, whereas PCT levels were higher in patients with severe sepsis or septic shock. In patients without infection, CRP did not correlate with eGFR, while PCT was negatively correlated with eGFR.ConclusionThis study demonstrates that CRP is accurate for predicting infection in patients with impaired renal function. The study suggests that in spite of its higher cost, PCT is not superior to CRP as an infection marker in terms of diagnostic value.
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Prognostic Factors and Oncological Outcomes of 122 Head and Neck Soft Tissue Sarcoma Patients Treated at a Single Institution.
Ann. Surg. Oncol.
PUBLISHED: 05-08-2014
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Head and neck soft tissue sarcomas (HNSTS) are rare tumors with various histological types displaying different clinical behavior. As a result, prognostic factors of this disease remain unclear. The aim of this study was to investigate the prognostic factors and oncological outcomes of HNSTS.
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Risk Factors for Recurrence of Papillary Thyroid Carcinoma with Clinically Node-Positive Lateral Neck.
Ann. Surg. Oncol.
PUBLISHED: 05-07-2014
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Papillary thyroid carcinoma (PTC) with clinically node-positive lateral neck is more likely to recur after surgery than node-negative PTC. The present study investigated the risk factors for recurrence in PTC patients with clinically node-positive lateral neck.
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C and N accumulations in soil aggregates determine nitrous oxide emissions from cover crop treated rice paddy soils during fallow season.
Sci. Total Environ.
PUBLISHED: 05-06-2014
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Combination of leguminous and non-leguminous plant residues are preferably applied in rice paddy soils to increase the rate of organic matter mineralization and to improve plant growth. However, organic matter addition facilitates methane (CH4) emission from rice paddy soil. Mineralization of organic nitrogen (N) increases NO3-N concentrations in soil, which are precursors for the formation of nitrous oxide (N2O). However, N2O is a minor greenhouse gas emitted from submerged rice field and hence is not often considered during calculation of total global warming potential (GWP) during rice cultivation. The hypothesis of this study was that fluxes of N2O emissions might be changed after removal of flooded water from rice field and the effect of cover crops on N2O emissions in the fallow season might be interesting. However, the effects of N-rich plant residues on N2O emission rates in the fallow season and its effect on annual GWP were not studied before. In this experiment, combination of barley (non-leguminous) and hairy vetch (leguminous) biomasses were applied at 9 Mg ha(-1) and 27 Mg ha(-1) rates in rice paddy soil. Cover crop application significantly increased CH4 emission flux while decreased N2O emissions during rice cultivation. The lowest N2O emission was observed in 27 Mg ha(-1) cover crop treated plots. Cover crop applications increased N contents in soil aggregates especially in smaller aggregates (<250 ?m), and that proportionately increased the N2O emission potentials of these soil aggregates. Fluxes of N2O emissions in the fallow season were influenced by the N2O emission potentials of soil aggregates and followed opposite trends as those observed during rice cultivation. Therefore, it could be concluded that the doses of cover crop applications for rice cultivation should not be optimized considering only CH4, but N2O should also be considered especially for fallow season to calculate total GWP.
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Clinical significance of pretreatment metabolic tumor volume and total lesion glycolysis in hypopharyngeal squamous cell carcinomas.
J Surg Oncol
PUBLISHED: 05-01-2014
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To evaluate the usefulness of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by pretreatment fluorine 18-fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET)/computed tomography (CT) as predictors of clinical outcome in hypopharyngeal squamous cell carcinoma (HPSCC).
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Prognostic stratification of brain metastases from hepatocellular carcinoma.
J. Neurooncol.
PUBLISHED: 04-18-2014
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The aim of this study is to evaluate prognostic factors of brain metastases from hepatocellular carcinoma. Medical records of 95 patients who have been diagnosed of brain metastases from hepatocellular carcinoma between January 2000 and December 2011 were retrospectively reviewed. The median age at diagnosis of brain metastases is 56.1 years. Eighty-two patients were male. Median interval from diagnosis of hepatocellular carcinoma to brain metastases was 29.5 months. Eighty-eight patents had extracranial metastases, and the lung was the most frequent involved organ. Motor weakness was the most frequent presenting symptom (49.5%). Intracranial hemorrhage was present in 71 patients (74.7%). Brain metastases were treated with whole brain radiation therapy (WBRT) alone in 57 patients, radiosurgery alone in 18, surgery and WBRT in 6, surgery and radiosurgery in 3, surgery alone in 3, radiosurgery and WBRT in 2, and conservative management only in 6. Median overall survival was 3.0 months. Multivariate analysis showed ECOG performance status, Child-Pugh class, AFP level, number of brain lesions, and treatment modality were associated with survival (p < 0.05). When patients were stratified with four prognostic factors including ECOG performance status, Child-Pugh class, AFP level, and number of brain lesions, median survival time for patients with 0-1, 2, 3-4 risk factors were 5.8 months, 2.5 months and 0.6 months, respectively (p < 0.001). In conclusion, we can estimate the survival of patients by prognostic stratification, although overall prognosis of patients with brain metastases from hepatocellular carcinoma is poor.
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Clinical values for abnormal ¹?F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma.
Eur J Radiol
PUBLISHED: 04-09-2014
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Fluorine 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in (18)F-FDG uptake. However, both physiologic and abnormal lesions increase (18)F-FDG uptake. Therefore, we evaluated (18)F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake.
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Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data.
Clin Mol Hepatol
PUBLISHED: 03-26-2014
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This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.
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Development of TRAIL resistance by radiation-induced hypermethylation of DR4 CpG island in recurrent laryngeal squamous cell carcinoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-26-2014
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There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis.
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Role of physical activity in nonalcoholic fatty liver disease in terms of visceral obesity and insulin resistance.
Liver Int.
PUBLISHED: 03-23-2014
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Limited evidence supports a role for physical activity (PA) in nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity or/and insulin resistance. We investigated the association between PA and NAFLD while considering visceral adipose tissue (VAT) and insulin resistance in a large general population.
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Postoperative stability for surgery-first approach using intraoral vertical ramus osteotomy: 12 month follow-up.
Br J Oral Maxillofac Surg
PUBLISHED: 03-14-2014
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The aim of this study was to evaluate the postoperative stability of the surgery-first approach using intraoral vertical ramus osteotomy (IVRO). We retrospectively studied a sample derived from the patients who were treated by the surgery-first approach using a LeFort I osteotomy and IVRO for correction of class III dentofacial deformity from 2008 to 2012. Lateral cephalograms taken preoperatively and 2 days, 6 months, and 12 months postoperatively were traced, and the skeletal and dental variables at different time points were analysed. The study sample comprised 37 subjects, mean (SD) age 23 (4) years. The mean (SD) total duration of treatment including postoperative orthodontics was 14 (6) months, and surgical movement of the maxillary A point was 0.75 (1.3)mm anteriorly, and 0.21 (1.79)mm superiorly. The surgical change in the position of the maxillary first molar was 1.01 (1.57)mm superiorly. The mean (SD) movement of mandible was 11.15 (5.4)mm posteriorly at pogonion and 1.02 (1.79)mm inferiorly at menton. There were no significant change in maxillary skeletal variables during the first year postoperative period. The surgical relapse of mandible at pogonion was 0.63 (2.31) mm anteriorly (p=0.01), however, the relapse in superior direction at menton was 2.86 (1.39) mm with statistical significance (p=0.01). The total duration of orthodontic treatment with surgery-first was roughly 5 months shorter than conventional preoperative and postoperative orthodontic treatment. The surgery-first approach using IVRO is effective and predictable, and shortens the overall duration of treatment. Anterior relapse of the mandible was less than 1mm, and increased superior relapse can be compensated for with appropriate preoperative planning to provide a reliable outcome. This study was limited to 12 months' follow-up, and a long term follow-up study is indicated.
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Autophagy inhibition can overcome radioresistance in breast cancer cells through suppression of TAK1 activation.
Anticancer Res.
PUBLISHED: 03-06-2014
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Autophagy is frequently activated in radioresistant cancer cells. In the present study, we evaluated the role of autophagy and transforming growth factor-activated kinase 1 (TAK1) in radioresistance.
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High ZT in p-type (PbTe)1-2x(PbSe)x(PbS)x thermoelectric materials.
J. Am. Chem. Soc.
PUBLISHED: 02-17-2014
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Lead chalcogenide thermoelectric systems have been shown to reach record high figure of merit values via modification of the band structure to increase the power factor or via nanostructuring to reduce the thermal conductivity. Recently, (PbTe)1-x(PbSe)x was reported to reach high power factors via a delayed onset of interband crossing. Conversely, the (PbTe)1-x(PbS)x was reported to achieve low thermal conductivities arising from extensive nanostructuring. Here we report the thermoelectric properties of the pseudoternary 2% Na-doped (PbTe)1-2x(PbSe)x(PbS)x system. The (PbTe)1-2x(PbSe)x(PbS)x system is an excellent platform to study phase competition between entropically driven atomic mixing (solid solution behavior) and enthalpy-driven phase separation. We observe that the thermoelectric properties of the PbTe-PbSe-PbS 2% Na doped are superior to those of 2% Na-doped PbTe-PbSe and PbTe-PbS, respectively, achieving a ZT ?2.0 at 800 K. The material exhibits an increased the power factor by virtue of valence band modification combined with a very reduced lattice thermal conductivity deriving from alloy scattering and point defects. The presence of sulfide ions in the rock-salt structure alters the band structure and creates a plateau in the electrical conductivity and thermopower from 600 to 800 K giving a power factor of 27 ?W/cmK(2). The very low total thermal conductivity values of 1.1 W/m·K of the x = 0.07 composition is accounted for essentially by phonon scattering from solid solution defects rather than the assistance of endotaxial nanostructures.
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Thermal- and photo-induced phase-transition behaviors of a tapered dendritic liquid crystal with photochromic azobenzene mesogens and a bicyclic chiral center.
Chemistry
PUBLISHED: 02-10-2014
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A ribbon-shaped chiral liquid crystalline (LC) dendrimer with photochromic azobenzene mesogens and an isosorbide chiral center (abbreviated as AZ3 DLC) was successfully synthesized and its major phase transitions were studied by using differential scanning calorimetry (DSC) and linear polarized optical microscopy (POM). Its ordered structures at different temperatures were further identified through structure-sensitive diffraction techniques. Based on the experimental results, it was found that the AZ3 DLC molecule exhibited the low-ordered chiral smectic (Sm*) LC phase with 6.31?nm periodicity at a high-temperature phase region. AZ3 DLC showed the reversible photoisomerization in both organic solvents and nematic (N) LC media. As a chiral-inducing agent, it exhibited a good solubility, a high helical-twisting power, and a large change in the helical-twisting power due to its photochemical isomerization in the commercially available N LC hosts. Therefore, we were able to reversibly "remote-control" the colors in the whole visible region by finely tuning the helical pitch of the spontaneously formed helical superstructures.
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Risk factors for central neck lymph node metastasis of clinically noninvasive, node-negative papillary thyroid microcarcinoma.
Am. J. Surg.
PUBLISHED: 02-10-2014
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To examine predictive factors for subclinical central neck lymph node metastases (LNM) of papillary thyroid microcarcinoma (PTMC).
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Small single-nodule hepatocellular carcinoma: comparison of transarterial chemoembolization, radiofrequency ablation, and hepatic resection by using inverse probability weighting.
Radiology
PUBLISHED: 02-08-2014
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To compare the effectiveness of transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and hepatic resection (HR) in patients with small single-nodule hepatocellular carcinoma by using inverse probability weighting to control selection bias.
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Oral delivery of a potent anti-angiogenic heparin conjugate by chemical conjugation and physical complexation using deoxycholic acid.
Biomaterials
PUBLISHED: 02-06-2014
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Angiogenesis, the formation of new blood vessels, plays a pivotal role in tumor progression and for this reason angiogenesis inhibitors are an important class of therapeutics for cancer treatment. Heparin-based angiogenesis inhibitors have been newly developed as one of such classes of therapeutics and possess a great promise in the clinical context. Taurocholate conjugated low molecular weight heparin derivative (LHT7) has been proven to be a potent, multi-targeting angiogenesis inhibitor against broad-spectrum angiogenic tumors. However, major limitations of LHT7 are its poor oral bioavailability, short half-life, and frequent parenteral dosing schedule. Addressing these issues, we have developed an oral formulation of LHT7 by chemically conjugating LHT7 with a tetrameric deoxycholic acid named LHTD4, and then physically complexing it with deoxycholylethylamine (DCK). The resulting LHTD4/DCK complex showed significantly enhanced oral bioavailability (34.3 ± 2.89%) and prolonged the mean residence time (7.5 ± 0.5 h). The LHTD4/DCK complex was mostly absorbed in the intestine by transcellular pathway via its interaction with apical sodium bile acid transporter. In vitro, the VEGF-induced sprouting of endothelial spheroids was significantly blocked by LHTD4. LHTD4/DCK complex significantly regressed the total vessel fractions of tumor (77.2 ± 3.9%), as analyzed by X-ray microCT angiography, thereby inhibiting tumor growth in vivo. Using the oral route of administration, we showed that LHTD4/DCK complex could be effective and chronically administered as angiogenesis inhibitor.
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Lymph node density as an independent predictor of cancer-specific mortality in patients with lymph node-positive laryngeal squamous cell carcinoma after laryngectomy.
Head Neck
PUBLISHED: 02-04-2014
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We examined the prognostic value of lymph node density in predicting cancer-specific mortality (CSM) for patients with lymph nodes positive (pN+) laryngeal squamous cell carcinoma (SCC) after laryngectomy.
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Increased risk of acute kidney injury associated with higher infusion rate of mannitol in patients with intracranial hemorrhage.
J. Neurosurg.
PUBLISHED: 01-31-2014
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Mannitol, an osmotic agent used to decrease intracranial pressure, can cause acute kidney injury (AKI). The objectives of this study were to assess the impact of mannitol on the incidence and severity of AKI and to identify risk factors and outcome for AKI in patients with intracranial hemorrhage (ICH).
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Radiofrequency ablation of hepatocellular carcinoma as first-line treatment: long-term results and prognostic factors in 162 patients with cirrhosis.
Radiology
PUBLISHED: 01-31-2014
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To evaluate the long-term outcomes of radiofrequency ablation (RFA) as a first-line therapy for early-stage hepatocellular carcinoma (HCC) and determine the prognostic factors for survival.
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18F fluorodeoxyglucose PET/CT in head and neck squamous cell carcinoma with negative neck palpation findings: a prospective study.
Radiology
PUBLISHED: 01-31-2014
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To assess the clinical usefulness of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and CT/magnetic resonance (MR) imaging in detecting occult neck metastasis in patients with head and neck squamous cell carcinoma and negative neck palpation findings.
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Tauroursodeoxycholic acid attenuates progression of steatohepatitis in mice fed a methionine-choline-deficient diet.
Dig. Dis. Sci.
PUBLISHED: 01-30-2014
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Endoplasmic reticulum (ER) stress has been implicated in the development of nonalcoholic steatohepatitis. A methionine-choline-deficient (MCD) diet induces robust ER stress response and steatohepatitis, but the effects of ER stress modulation on the course of steatohepatitis remain uncertain. The present study evaluated whether reducing ER stress using the chemical chaperone tauroursodeoxycholic acid (TUDCA) could limit hepatocyte lipoapoptosis and progression of MCD diet-induced steatohepatitis.
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Aspiration cytology of mammary analogue secretory carcinoma of the salivary gland.
Diagn. Cytopathol.
PUBLISHED: 01-22-2014
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Aspiration cytologic findings of mammary analogue secretory carcinoma (MASC), a newly established salivary gland neoplasm defined by a t(12;15)(p13;q25) ETV6-NTRK3 translocation, are not fully characterized to date. We report cytologic descriptions of nine cases of molecularly confirmed MASC, including two with unusual findings.
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Hepatitis B viral load affects prognosis of hepatocellular carcinoma.
World J. Gastroenterol.
PUBLISHED: 01-20-2014
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Hepatocellular carcinoma (HCC) is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself. The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function. Hepatitis B virus (HBV) is an established major risk factor of HCC development, and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC. High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways. First, it is associated with more frequent recurrence of HBV-related HCC after treatment. Second, it is associated with more occurrence and severity of potentially life-threatening HBV reactivation. Last, it is associated with more worsened liver function, which limits the therapeutic options for HBV-related HCC. HBV, directly or indirectly, can induce hepatocarcinogenesis. In patients with a high HBV DNA level and subsequent active hepatitis, adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis. HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes. Thus, high HBV viral load can affect the prognosis of patients with HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression. Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC. Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression, it is expected that long-term antiviral therapy results in the sustained HBV suppression, control of inflammation, reduction in HCC progression, and eventually in improved overall survival.
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Short-Term Treatment Results for Unilateral Vocal Fold Palsy Induced by Mediastinal Lesions.
J Voice
PUBLISHED: 01-14-2014
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Vocal fold paralysis (VFP) is a frequent complication of surgery of mediastinal structures. This study evaluated the characteristics and short-term treatment outcomes of injection laryngoplasty for unilateral VFP (UVFP) induced by mediastinal lesions.
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Prior exposure to lamivudine increases entecavir resistance risk in chronic hepatitis B Patients without detectable lamivudine resistance.
Antimicrob. Agents Chemother.
PUBLISHED: 01-06-2014
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The efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1, n=142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2, n=233), and patients with LAM-R when starting ETV (group 3, n=125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR]=14.4, P<0.001) but also in group 2 (HR=5.0, P<0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR=13.0, P=0.013) as well as group 3 (HR=43.9, P<0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.
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Does antiviral therapy reduce complications of cirrhosis?
World J. Gastroenterol.
PUBLISHED: 01-02-2014
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Chronic hepatitis B infection is associated with the development of cirrhosis, hepatocellular carcinoma, and finally liver-related mortality. Each year, approximately, 2%-5% of patients with hepatitis B virus (HBV)-related compensated cirrhosis develop decompensation, with additional clinical manifestations, such as ascites, jaundice, hepatic encephalopathy, and gastrointestinal bleeding. The outcome of decompensated HBV-related cirrhosis is poor, with a 5-year survival of 14%-35% compared to 84% in patients with compensated cirrhosis. Because the risk of disease progression is closely linked to a patient's serum HBV DNA level, antiviral therapy may suppress viral replication, stabilize liver function and improve survival. This article briefly reviews the role that antiviral therapy plays in cirrhosis complications, particularly, in decompensation and acute-on-chronic liver failure.
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Spontaneous evolution in bilirubin levels predicts liver-related mortality in patients with alcoholic hepatitis.
PLoS ONE
PUBLISHED: 01-01-2014
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The accurate prognostic stratification of alcoholic hepatitis (AH) is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort) and 106 patients with AH between 2005 and 2012 (a validation cohort). The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL) were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC). For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001). In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment.
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Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Primary tumor and tumor-associated metastatic lymphatics have emerged as new targets for anticancer therapy, given that these are difficult to treat using traditional chemotherapy. In this study, docetaxel-loaded Pluronic nanoparticles with Flamma (FPR-675, fluorescence molecular imaging dye; DTX/FPR-675 Pluronic NPs) were prepared using a temperature-induced phase transition for accurate detection of metastatic lymphatics. Significant accumulation was seen at the primary tumor and in metastatic lymph nodes within a short time. Particle size, maximum drug loading capacity, and drug encapsulation efficiency of the docetaxel-loaded Pluronic NPs were approximately 10.34±4.28 nm, 3.84 wt%, and 94±2.67 wt%, respectively. Lymphatic tracking after local and systemic delivery showed that DTX/FPR-675 Pluronic NPs were more potent in tumor-bearing mice than in normal mice, and excised mouse lymphatics showed stronger near-infrared fluorescence intensity on the tumor-bearing side than on the non-tumor-bearing side at 60 minutes post-injection. In vivo cytotoxicity and efficacy data for the NPs demonstrated that the systemically administered NPs caused little tissue damage and had minimal side effects in terms of slow renal excretion and prolonged circulation in tumor-bearing mice, and rapid renal excretion in non-tumor-bearing mice using an in vivo real-time near-infrared fluorescence imaging system. These results clearly indicate that docetaxel-loaded Pluronic NPs could provide a strategy to achieve effective cancer therapy by simultaneous delivery to primary tumors, tumor lymphatics, and tumor-associated metastatic lymphatics.
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Serum insulin-like growth factor-1 predicts disease progression and survival in patients with hepatocellular carcinoma who undergo transarterial chemoembolization.
PLoS ONE
PUBLISHED: 01-01-2014
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Insulin like-growth factor-1 (IGF-1) reflects hepatic synthetic function and plays a major role in the development and progression of various cancers. In the present study, we investigated whether baseline serum IGF-1 levels predict time-to-progression (TTP) and overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). A total of 155 consecutive treatment-naive patients with HCC who had undergone TACE as initial treatment were included from a prospective cohort. Baseline serum IGF-1 levels were analyzed with regard to their associations with disease progression and survival. During a median follow-up period of 41.8 months, patients with low IGF-1 levels showed significantly shorter TTP (median, 6.0 months; 95% confidence interval [CI], 4.5-7.6) than patients with high IGF-1 levels (median, 16.5 months; 95% CI, 4.9-28.1; p?=?0.003). In the multivariate analysis, BCLC stage, serum vascular endothelial growth factorlevels, and IGF-1 levels were independent risk factors for disease progression. The hazard ratio (HR) of progression for each 10 ng/mL decrease in IGF-1 level was 1.072 (95% CI, 1.029-1.117; p?=?0.001). Furthermore, together with tumor size, stage, and treatment response, IGF-1 levels were an independent predictor of poorer survival (for each 10 ng/mL decrease in IGF-1 level; HR, 1.057; 95% CI, 1.001-1.115; p?=?0.045). In conclusion, low baseline IGF-1 levels independently correlated with shorter TTP and poorer OS in patients with HCC who underwent TACE.
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Nonalcoholic fatty liver disease is a negative risk factor for prostate cancer recurrence.
Endocr. Relat. Cancer
PUBLISHED: 01-01-2014
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Nonalcoholic fatty liver disease (NAFLD) is closely related to the metabolic syndrome, which is associated with an increased risk of various malignancies. In this study, we investigated the association between NAFLD and prostate cancer biochemical recurrence (BCR) after radical prostatectomy. Consecutive prostate cancer patients who underwent radical prostatectomy were enrolled from two hospitals in Korea and randomly assigned to the training (n=147) or validation set (n=146). The presence of NAFLD, BMI, preoperative prostate-specific antigen, and histological findings including Gleason score (GSc) were analyzed in regard to their association with BCR. NAFLD was diagnosed based on ultrasonography or unenhanced computed tomography images. BCR-free survival rates were calculated using the Kaplan-Meier method. In the training set, 32 (21.8%) patients developed BCR during a median follow-up period of 51 (inter-quartile range, 35-65) months. In the multivariate analysis, the presence of NAFLD (hazard ratio (HR), 0.36; 95% CI, 0.14-0.97; P=0.04) was an independent negative predictive factor of BCR after adjustment for pathological GSc. Applied to the validation set, the presence of NAFLD maintained its prognostic value for longer time-to-BCR (HR, 0.17; 95% CI, 0.06-0.49; P=0.001). In the subgroup analysis of patients with NAFLD, NAFLD fibrosis score was a single independent negative predictor for BCR (HR, 0.54; 95% CI, 0.30-0.98; P=0.04). Our study demonstrated that NAFLD may play a protective role against BCR after radical prostatectomy for prostate cancer. Further study is warranted to elucidate the mechanism of protective effect in patients with NAFLD.
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Complex adaptive therapeutic strategy (CATS) for cancer.
J Control Release
PUBLISHED: 11-04-2013
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Tumors begin with a single cell, but as each tumor grows and evolves, it becomes a wide collection of clones that display remarkable heterogeneity in phenotypic features, which has posed a big challenge to current targeted anticancer therapy. Intra- and inter-tumoral heterogeneity is attributable in part to genetic mutations but also to adaptation and evolution of tumors to heterogeneity in tumor microenvironments. If tumors are viewed not only as a disease but also as a complex adaptive system (CAS), tumors should be treated as such and a more systemic approach is needed. Some of many tumors therapeutic strategies are discussed here from a view of a tumor as CAS, which can be collectively called a complex adaptive therapeutic strategy (CATS). The central theme of CATS is based on three intermediate concepts: i) disruption of artifacts, ii) disruption of connections, and iii) reprogramming of cancer-immune dynamics. Each strategy presented here is a piece of the puzzle for CATS. Although each piece by itself may be neither novel nor profound, an assembled puzzle could be a novel and innovative cancer therapeutic strategy.
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MicroRNA-196A-2 polymorphisms and hepatocellular carcinoma in patients with chronic hepatitis B.
J. Med. Virol.
PUBLISHED: 10-16-2013
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Single nucleotide polymorphisms (SNPs) in microRNA (miR)-196a-2 have been suggested to contribute to susceptibility to various human cancers. The aim of this study was to determine whether polymorphisms of miRNA-196a-2 affect the clinical outcomes of hepatitis B virus (HBV) infection in Korean patients. Genotyping was performed for 1,439 Korean patients with either past or present HBV infection, including 404 control subjects who underwent spontaneous recovery and 1,035 subjects with chronic HBV (313 cases of chronic hepatitis B, 305 cases of cirrhosis of the liver, and 417 cases of hepatocellular carcinoma [HCC]). Genotyping results revealed that the polymorphism rs12304647A>C, which lies in the pri-miRNA region of miR-196a-2, has a significant minor allele frequency (0.210). Logistic analysis revealed that the rs12304647A>C SNP was associated with a significant protective effect against HCC in patients with chronic hepatitis (odds ratio [OR]?=?0.70, P?=?0.005 in a codominant model; OR?=?0.73, P?=?0.03 in a dominant model; OR?=?0.31, P?=?0.004 in a recessive model), and in the patients with cirrhosis (OR?=?0.63, P?=?0.0009 in a codominant model; OR?=?0.66, P?=?0.01 in a dominant model; OR?=?0.25, P?=?0.001 in a recessive model). A Cox relative hazards model with adjustments for age, gender, HBeAg status, and cirrhosis revealed that rs12304647A>C retained its association with HCC in a codominant model (relative hazards [RH]?=?1.14, P?=?0.05) and in a recessive model (RH?=?1.44, P?=?0.03). However, the miR-196a-2 rs12304647A>C SNP had no association with HBV clearance. In conclusion, the miR-196a-2 rs12304647 CC genotype had a protective effect against development of HCC in comparison to the AA or AC genotypes in patients with chronic hepatitis and cirrhosis. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
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Efficacy of adefovir-based combination therapy for patients with Lamivudine- and entecavir-resistant chronic hepatitis B virus infection.
Antimicrob. Agents Chemother.
PUBLISHED: 10-07-2013
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Treatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB) patients are not yet well established. The aim of this study was to evaluate overall antiviral efficacy and to compare the efficacy of combination therapy with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus (HBV) variants. Virologic, biochemical, and serologic responses during combination therapy with ADV plus nucleoside analogues were assessed. Propensity score analysis was used to select a matched group of patients for the comparison of rescue therapy regimens. A total of 67 consecutive patients were analyzed. Complete virologic suppression was achieved in 27 patients. The overall cumulative incidence of complete virologic suppression at month 24 was 47.4%: 44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV. There was no significant difference between these two groups (P = 0.234). The cumulative incidences of complete virologic suppression were still comparable between the two groups selected and matched using the propensity score model (P = 0.419). Virologic breakthrough was observed in 9 patients, and rtA181V substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg) negativity and lower baseline HBV DNA level were associated with complete virologic suppression in univariate analysis. In multivariate analysis, lower baseline HBV DNA level remained an independent predictor. In conclusion, combination therapy with ADV plus nucleoside analogues fails to show sufficient antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further study is warranted to evaluate the efficacy of a more potent tenofovir-based regimen in such patients.
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Sodium taurocholate cotransporting polypeptide mediates dual actions of deoxycholic acid in human hepatocellular carcinoma cells: enhanced apoptosis versus growth stimulation.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 10-01-2013
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The hydrophobic bile acid, deoxycholic acid (DC), can induce apoptosis in hepatocytes. The roles of DC and its transporter are not yet established in hepatocellular carcinoma (HCC) cells. We investigated DC-induced alterations in HCC cell growth, with a particular focus on the effect of the expression of bile acid (BA)-transporting Na(+)-dependent taurocholic cotransporting polypeptides (NTCPs).
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Lymph Node Ratio of the Central Compartment is a Significant Predictor for Locoregional Recurrence After Prophylactic Central Neck Dissection in Patients with Thyroid Papillary Carcinoma.
Ann. Surg. Oncol.
PUBLISHED: 09-05-2013
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Lymph node ratio (LNR) is an important prognosis factor in many solid cancers, but there have been few reports of LNR in papillary thyroid carcinoma (PTC). This study investigated LNR of the central compartment to determine whether LNR has clinical significance as a prognostic predictor for recurrence after prophylactic central neck dissection (pCND) in patients with PTC.
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Oligomeric bile acid-mediated oral delivery of low molecular weight heparin.
J Control Release
PUBLISHED: 09-04-2013
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Intestinal transporters are limited to the transport of small molecular substrates. Here, we describe the development of apical sodium-dependent bile acid transporter (ASBT)-targeted high-affinity oligomeric bile acid substrates that mediate the transmembrane transport of low molecular weight heparin (LMWH). Several oligomers of deoxycholic acid (oligoDOCA) were synthesized to investigate the substrate specificity of ASBT. To see the binding of oligoDOCA on the substrate-binding pocket of ASBT, molecular docking was used and the dissociation rate constants (KD) were measured using surface plasmon resonance. The KD for tetrameric DOCA (tetraDOCA) was 50-fold lower than that for monomeric DOCA, because tetraDOCA interacted with several hydrophobic grooves in the substrate-binding pocket of ASBT. The synthesized oligoDOCA compounds were subsequently chemically conjugated to macromolecular LMWH. In vitro, tetraDOCA-conjugated LMWH (LHe-tetraD) had highest selectivity for ASBT during its transport. Orally administered LHe-tetraD showed remarkable systemic anticoagulation activity and high oral bioavailability of 33.5±3.2% and 19.9±2.5% in rats and monkeys, respectively. Notably, LHe-tetraD successfully prevented thrombosis in a rat model of deep vein thrombosis. These results represent a major advancement in ASBT-mediated LMWH delivery and may facilitate administration of many important therapeutic macromolecules through a non-invasive oral route.
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Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence.
Autophagy
PUBLISHED: 08-13-2013
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Radiotherapy is one of the well-established therapeutic modalities for cancer treatment. However, the emergence of cells refractory to radiation is a major obstacle to successful treatment with radiotherapy. Many reports suggest that inhibitors targeting the mechanistic target of rapamycin (MTOR) can sensitize cancer cells to the effect of radiation, although by which mechanism MTOR inhibitors enhance the efficacy of radiation toward cancer cells remains to be elucidated. Our studies indicate that a potent and persistent activation of autophagy via inhibition of the MTOR pathway, even in cancer cells where autophagy is occurring, can trigger premature senescence, cellular proliferation arrest. Combined treatment of MTOR inhibitor and radiation induce heterochromatin formation, an irreversible growth arrest and an increase of senescence-associated GLB1 (?-galactosidase) activity, which appear to result from a constant activation of TP53 and a restoration in the activity of retinoblastoma 1 protein (RB1)-E2F1. Thus, this study provides evidence that promoting cellular senescence via inhibition of the MTOR pathway may serve as an avenue to augment radiosensitivity in cancer cells that initiate an autophagy-survival mode to radiotherapy.
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Technical considerations for large-scale parallel reaction monitoring analysis.
J Proteomics
PUBLISHED: 07-29-2013
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Targeted methods have gained acceptance among proteomics community to perform quantitative experiments. However, the current reference to conduct such experiments relies on selected reaction monitoring (SRM) analyses performed on triple quadrupole mass spectrometers, although it suffers from some limitations. First, the low resolution quadrupole mass analyzers do not present enough selectivity to discriminate the analytes from interferences commonly encountered in biological samples. Second, the number of peptides monitored in one single experiment often remains limited. The introduction of high resolution/accurate mass instruments with fast sequencing capabilities has enabled the development of novel quantitative methods. More specifically, the new quadrupole-orbitrap mass spectrometer operated in parallel reaction monitoring (PRM) mode showed detection and quantification performances similar or better than those obtained in SRM, due to the increased selectivity of the high-resolution orbitrap mass analyzer. The versatility of the instrument, with its ability to multiplex the selection of precursor ions and to operate with varying quadrupole isolation windows, has enabled the design of large-scale experiments, which require the optimization of several acquisition parameters to maintain high performance. It includes the adjustments of the fill time of the trapping device and the tight scheduling of elution times of the peptides, ideally adjusted on-the-fly.
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Interleukin-8 is related to poor chemotherapeutic response and tumourigenicity in hepatocellular carcinoma.
Eur. J. Cancer
PUBLISHED: 07-03-2013
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Interleukin-8 (IL-8) has been suggested as a prognostic biomarker for human hepatocellular carcinoma (HCC), but its roles in HCC progression and drug resistance have not been studied. This study investigates the role and underlying mechanism of IL-8 in the chemoresistance and progressive growth of HCC.
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Second cancer incidence, risk factor, and specific mortality in head and neck squamous cell carcinoma.
Otolaryngol Head Neck Surg
PUBLISHED: 07-02-2013
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Second primary malignancies (SPMs) are common in patients with head and neck squamous cell carcinoma (HNSCC) and have a negative impact on their survival. This study aimed to evaluate risk factors for SPM occurrence and cause-specific mortality in Asian HNSCC patients.
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Prognostic factors in patients with head and neck squamous cell carcinoma with cN3 neck disease: a retrospective case-control study.
Oral Surg Oral Med Oral Pathol Oral Radiol
PUBLISHED: 06-27-2013
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This study examined prognostic factors in patients with head and neck squamous cell carcinoma with advanced neck disease.
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ARS-interacting multi-functional protein 1 induces proliferation of human bone marrow-derived mesenchymal stem cells by accumulation of ?-catenin via fibroblast growth factor receptor 2-mediated activation of Akt.
Stem Cells Dev.
PUBLISHED: 06-25-2013
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ARS-Interacting Multi-functional Protein 1 (AIMP1) is a cytokine that is involved in the regulation of angiogenesis, immune activation, and fibroblast proliferation. In this study, fibroblast growth factor receptor 2 (FGFR2) was isolated as a binding partner of AIMP peptide (amino acids 6-46) in affinity purification using human bone marrow-derived mesenchymal stem cells (BMMSCs). AIMP1 peptide induced the proliferation of adult BMMSCs by activating Akt, inhibiting glycogen synthase kinase-3?, and thereby increasing the level of ?-catenin. In addition, AIMP1 peptide induced the translocation of ?-catenin to the nucleus and increased the transcription of c-myc and cyclin D1 by activating the ?-catenin/T-cell factor (TCF) complex. By contrast, transfection of dominant negative TCF abolished the effect of AIMP1. The inhibition of Akt, using LY294002, abolished the accumulation and nuclear translocation of ?-catenin induced by AIMP1, leading to a decrease in c-myc and cyclin D1 expression, which decreased the proliferation of BMMSCs. An intraperitoneal injection of AIMP1 peptide into C57/BL6 mice increased the colony formation of fibroblast-like cells. Fluorescence activated cell sorting analysis showed that the colony-forming cells were CD29(+)/CD44(+)/CD90(+)/CD105(+)/CD34(-)/CD45(-), which is characteristic of MSCs. In addition, the fibroblast-like cells differentiated into adipocytes, chondrocytes, and osteocytes. Taken together, these data suggest that AIMP1 peptide promotes the proliferation of BMMSCs by activating the ?-catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in MSCs in peripheral blood.
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Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by (18)F-FDG PET/CT in squamous cell carcinoma of the oral cavity.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 06-23-2013
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Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by (18)F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC.
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Basal cell adenocarcinoma of the salivary gland: a morphological and immunohistochemical comparison with basal cell adenoma with and without capsular invasion.
Diagn Pathol
PUBLISHED: 06-17-2013
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It is often difficult to diagnose salivary gland tumors that exhibit basaloid features differentially. The aim of this study was to identify additional morphological and immunohistochemical characteristics that can aid the diagnosis of basal cell adenocarcinoma (BCAC) of the salivary gland. Methods and results: In total, 29 basal cell neoplasms [eight BCACs, 11 basal cell adenomas (BCAs) with capsular invasion, and 10 BCAs without capsular invasion] and 10 cases of adenoid cystic carcinomas (ACCs) were subjected to histopathology and immunohistochemical analyses for CK7, CK5/6, SMA, p63, calponin, p53, c-erbB2, CD117, beta-catenin, EGFR, VEGF, Ki-67, and S100P protein expression. Compared to BCA without capsular invasion, the BCACs and BCAs with capsular invasion were more likely to be larger and have solid or cribriform patterns. Most BCACs and BCAs exhibited nuclear beta-catenin expression. In all basal cell neoplasm cases, the clinical course after surgery with or without radiotherapy was indolent. beta-catenin, CK5/6, CD117, and S100P protein were helpful for differentiating basal cell neoplasms from ACC.
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Patients with persistent new-onset diabetes after transplantation have greater weight gain after kidney transplantation.
J. Korean Med. Sci.
PUBLISHED: 06-17-2013
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The purpose of the present study was to evaluate the difference in BMI pattern between patients with persistent new-onset diabetes after transplantation (P-NODAT) and without new-onset diabetes after transplantation (N-NODAT) in a retrospective matched case-control (1:3) analysis. Thirty-six patients who developed P-NODAT were identified among 186 adult renal transplant recipients with no evidence of pretransplant diabetes mellitus who underwent kidney transplantation from September 1997 to March 2008 and were treated with a triple regimen including tacrolimus. The controls were selected to match the patients for pretransplant BMI, age at transplantation (± 5 yr), and date of transplantation (± 12 months). Finally, 20 P-NODAT patients and 60 N-NODAT patients were selected. The pre- and posttransplant BMI data were collected every 16 weeks for up to 80 weeks. The clinical characteristics did not differ between the P-NODAT group and N-NODAT group. BMI increased faster in the P-NODAT group than in the N-NODAT group. The mixed-model analysis showed that patients with P-NODAT exhibited a faster increase in BMI. P-NODAT is associated with posttransplant weight gain. The risk of P-NODAT should be considered in patients with rapid weight gain after transplantation.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.