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Find video protocols related to scientific articles indexed in Pubmed.
The chemokine (CCL2-CCR2) signaling axis mediates perineural invasion.
Mol. Cancer Res.
PUBLISHED: 10-15-2014
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Perineural invasion (PNI) is a form of cancer progression where cancer cells invade along nerves. This behavior is associated with poor clinical outcomes; therefore, it is critical to identify novel ligand-receptor interactions between nerves and cancer cells that support the process of PNI. A proteomic profiler chemokine array was used to screen for nerve-derived factors secreted from tissue explants of dorsal root ganglion (DRG), and CCL2 was identified as a lead candidate. Prostate cancer cell line expression of CCR2, the receptor to CCL2, correlated closely with MAPK and Akt pathway activity and cell migration towards CCL2 and DRG. In vitro nerve and cancer co-culture invasion assays of PNI demonstrated that cancer cell CCR2 expression facilitates PNI. PNI is significantly diminished in co-culture assays when using DRG harvested from CCL2-/- knockout mice as compared with control CCL2+/+ mice, indicating that CCR2 is required for PNI in this murine model of PNI. Furthermore, 20/21 (95%) of patient specimens of prostate adenocarcinoma with PNI exhibited CCR2 expression by immunohistochemistry, while just 3/13 (23%) lacking PNI expressed CCR2. In summary, nerve-released CCL2 supports prostate cancer migration and PNI though CCR2-mediated signaling. Implications: These results reveal CCL2-CCR2 signaling as a key ligand-receptor mechanism that mediates cancer cell communication with nerves during PNI and highlight a potential future therapeutic target.
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Discovery of 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an antidiabetic clinical candidate targeting GPR119.
J. Med. Chem.
PUBLISHED: 09-10-2014
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G-protein-coupled receptor 119 (GPR119) is expressed predominantly in pancreatic ?-cells and in enteroendocrine cells in the gastrointestinal tract. GPR119 agonists have been shown to stimulate glucose-dependent insulin release by direct action in the pancreas and to promote secretion of the incretin GLP-1 by action in the gastrointestinal tract. This dual mechanism of action has generated significant interest in the discovery of small molecule GPR119 agonists as a potential new treatment for type 2 diabetes. Herein, we describe the discovery and optimization of a new class of pyridone containing GPR119 agonists. The potent and selective BMS-903452 (42) was efficacious in both acute and chronic in vivo rodent models of diabetes. Dosing of 42 in a single ascending dose study in normal healthy humans showed a dose dependent increase in exposure and a trend toward increased total GLP-1 plasma levels.
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Antiphospholipid antibody testing for the antiphospholipid syndrome: a comprehensive practical review including a synopsis of challenges and recent guidelines.
Pathology
PUBLISHED: 08-28-2014
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The antiphospholipid (antibody) syndrome (APS) is an autoimmune condition characterised by a wide range of clinical features, but primarily identified as thrombotic and/or obstetric related adverse events. APS is associated with the presence of antiphospholipid antibodies (aPL), including the so-called lupus anticoagulant (LA). These aPL are heterogeneous in nature, detected with varying sensitivity and specificity by a diverse range of laboratory tests. All these tests are unfortunately imperfect, suffer from poor assay reproducibility (inter-method and inter-laboratory) and a lack of standardisation and harmonisation. Clinicians and laboratory personnel may struggle to keep abreast of these factors, as well as the expanding range of available aPL tests, and consequent result interpretation. Therefore, APS remains a significant diagnostic challenge for many clinicians across a wide range of clinical specialities, due to these issues related to laboratory testing as well as the ever-expanding range of reported clinical manifestations. This review is primarily focussed on issues related to laboratory testing for APS in regards to the currently available assays, and summarises recent international consensus guidelines for aPL testing, both for the liquid phase functional LA assays and the solid phase assays (anticardiolipin and anti-beta-2-Glycoprotein-I).
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A nomogram to predict loco-regional control after re-irradiation for head and neck cancer.
Radiother Oncol
PUBLISHED: 05-26-2014
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Loco-regionally recurrent head and neck cancer (HNC) in the setting of prior radiotherapy carries significant morbidity and mortality. The role of re-irradiation (re-RT) remains unclear due to toxicity. We determined prognostic factors for loco-regional control (LRC) and formulated a nomogram to help clinicians select re-RT candidates.
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GFR?1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-28-2014
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The ability of cancer cells to invade along nerves is associated with aggressive disease and diminished patient survival rates. Perineural invasion (PNI) may be mediated by nerve secretion of glial cell line-derived neurotrophic factor (GDNF) attracting cancer cell migration through activation of cell surface Ret proto-oncogene (RET) receptors. GDNF family receptor (GFR)?1 acts as coreceptor with RET, with both required for response to GDNF. We demonstrate that GFR?1 released by nerves enhances PNI, even in the absence of cancer cell GFR?1 expression. Cancer cell migration toward GDNF, RET phosphorylation, and MAPK pathway activity are increased with exposure to soluble GFR?1 in a dose-dependent fashion. Dorsal root ganglia (DRG) release soluble GFR?1, which potentiates RET activation and cancer cell migration. In vitro DRG coculture assays of PNI show diminished PNI with DRG from GFR?1(+/-) mice compared with GFR?1(+/+) mice. An in vivo murine model of PNI demonstrates that cancer cells lacking GFR?1 maintain an ability to invade nerves and impair nerve function, whereas those lacking RET lose this ability. A tissue microarray of human pancreatic ductal adenocarcinomas demonstrates wide variance of cancer cell GFR?1 expression, suggesting an alternate source of GFR?1 in PNI. These findings collectively demonstrate that GFR?1 released by nerves enhances PNI through GDNF-RET signaling and that GFR?1 expression by cancer cells enhances but is not required for PNI. These results advance a mechanistic understanding of PNI and implicate the nerve itself as a key facilitator of this adverse cancer cell behavior.
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External beam radiotherapy with or without concurrent chemotherapy in advanced or recurrent non-anaplastic non-medullary thyroid cancer.
J Surg Oncol
PUBLISHED: 04-25-2014
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To review clinical outcomes and toxicities in locally advanced differentiated thyroid cancer patients treated with external beam radiotherapy (EBRT) with or without concurrent chemotherapy (CCRT).
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Epithelial-mesenchymal transition enhances response to oncolytic herpesviral therapy through nectin-1.
Hum. Gene Ther.
PUBLISHED: 04-02-2014
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Cancers exhibiting epithelial-mesenchymal transition (EMT) are associated with aggressive behavior and increased metastatic potential. Therapies that are able to target EMT would have significant clinical value. Nectin-1 is a cell surface herpes simplex virus type 1 (HSV-1) receptor that also forms a component of intercellular adherens junctions, which are typically disrupted in EMT. To explore relationships between HSV-1 sensitivity and EMT, we generated cell lines with a stable EMT phenotype from human follicular thyroid cancer (WRO82-1) through E-cadherin silencing with short hairpin RNA (shEcadWRO). HSV-1 viral attachment and gene expression were both enhanced in shEcadWRO as compared with shControl. Immunoblotting and immunostaining revealed enhanced nectin-1 expression by shEcadWRO. Receptor-blocking assays demonstrated that increased herpesviral entry into shEcadWRO as compared with shControl was mediated predominantly through nectin-1. Colocalization of green fluorescent protein-tagged HSV-1 and tdTomato-tagged nectin-1 confirmed an increase in viral attachment to nectin-1 in shEcadWRO. Cell viability assays demonstrated increased susceptibility of shEcadWRO to HSV-1 oncolysis, and a murine flank tumor model showed significantly enhanced regression of shEcadWRO tumors in response to oncolytic HSV-1 as compared with control tumors. A separate model of EMT induction through transforming growth factor-? stimulation confirmed enhanced HSV-1 susceptibility in Panc1 cells. These results demonstrate that the process of EMT leads to increased herpesviral susceptibility through enhanced cell surface nectin-1 expression, suggesting that cancers exhibiting EMT may be naturally sensitive targets for herpesviral therapy.
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Irradiation for locoregionally recurrent, never-irradiated oral cavity cancers.
Head Neck
PUBLISHED: 03-30-2014
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The purpose of this study was to report the clinical outcomes and related prognostic factors of patients who underwent radiotherapy (RT) for the treatment of recurrent, never-irradiated oral cavity cancer (recurrent OCC).
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Patients with low lying lymph nodes are at high risk for distant metastasis in oropharyngeal cancer.
Oral Oncol.
PUBLISHED: 03-26-2014
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We sought to identify risk factors for distant metastasis (DM) in patients with oropharyngeal cancer (OPC) and perform a recursive partition analysis (RPA) to identify patients both at low and high risk for DM.
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Results of a prospective thyroid ultrasound screening program in adenomatous polyposis patients.
Am. J. Surg.
PUBLISHED: 03-23-2014
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Patients with adenomatous polyposis may be at increased risk for developing thyroid cancer (TC). However, screening guidelines for TC in these patients are not well established.
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Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy's local control superior?
Radiol Oncol
PUBLISHED: 03-01-2014
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The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980's reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution's results of photon radiotherapy for unresectable salivary gland tumors.
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A silk-elastinlike protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus.
Head Neck
PUBLISHED: 02-19-2014
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Background: Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately following surgical resection. Methods: Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastinlike protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. Results: GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in PBS, and at one week retains a thousand fold greater infectious plaque forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and show increased viral ?-galactosidase expression as compared to PBS. Conclusions: The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes. Head Neck, 2014.
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Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck.
Am. J. Clin. Oncol.
PUBLISHED: 01-10-2014
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We previously reported inferior outcomes for locally advanced head and neck cancer treated with cetuximab (C225) versus cisplatin (CDDP). We now examine if this difference persists when accounting for HPV status and update outcomes on the entire cohort.
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Nomograms for preoperative prediction of prognosis in patients with oral cavity squamous cell carcinoma.
Cancer
PUBLISHED: 01-09-2014
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This study sought to develop prognostic tools that will accurately predict overall and cancer-related mortality and risk of recurrence in individual patients with oral cancer based on host and tumor characteristics. These tools would take into account numerous prognosticators beyond those covered by the traditional TNM (tumor-node-metastasis) staging system.
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Reduction of Tendon Adhesions following Administration of Adaprev, a Hypertonic Solution of Mannose-6-Phosphate: Mechanism of Action Studies.
PLoS ONE
PUBLISHED: 01-01-2014
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Repaired tendons may be complicated by progressive fibrosis, causing adhesion formation or tendon softening leading to tendon rupture and subsequent reduced range of motion. There are few therapies available which improve the gliding of damaged tendons in the hand. We investigate the role of Mannose 6-phosphate (M6P) in a 600 mM hypertonic solution (Adaprev) on tendon adhesion formation in vivo using a mouse model of severed tendon in conjunction with analysis of collagen synthesis, cellular proliferation and receptors involved in TGF beta signalling. Cytotoxicity was assessed by measuring tissue residency, mechanical strength and cell viability of tendons after treatment with Adaprev. To elicit potential modes of action, in vitro and ex vivo studies were performed investigating phosphorylation of p38, cell migration and proliferation. Adaprev treatment significantly (p<0.05) reduced the development of adhesions and improved collagen organisation without reducing overall collagen synthesis following tendon injury in vivo. The bioavailability of Adaprev saw a 40% reduction at the site of administration over 45 minutes and tendon fibroblasts tolerated up to 120 minutes of exposure without significant loss of cell viability or tensile strength. These favourable effects were independent of CI-MPR and TGF-? signalling and possibly highlight a novel mechanism of action related to cellular stress demonstrated by phosphorylation of p38. The effect of treatment reduced tendon fibroblast migration and transiently halted tendon fibroblast proliferation in vitro and ex vivo. Our studies demonstrate that the primary mode of action for Adaprev is potentially via a physical, non-chemical, hyperosmotic effect.
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Nucleoporin Nup62 maintains centrosome homeostasis.
Cell Cycle
PUBLISHED: 10-07-2013
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Centrosomes are comprised of 2 orthogonally arranged centrioles surrounded by the pericentriolar material (PCM), which serves as the main microtubule organizing center of the animal cell. More importantly, centrosomes also control spindle polarity and orientation during mitosis. Recently, we and other investigators discovered that several nucleoporins play critical roles during cell division. Here, we show that nucleoporin Nup62 plays a novel role in centrosome integrity. Knockdown of Nup62 induced mitotic arrest in G 2/M phases and mitotic cell death. Depletion of Nup62 using RNA interference results in defective centrosome segregation and centriole maturation during the G 2 phase. Moreover, Nup62 depletion in human cells leads to the appearance of multinucleated cells and induces the formation of multipolar centrosomes, centriole synthesis defects, dramatic spindle orientation defects, and centrosome component rearrangements that impair cell bi-polarity. Our results also point to a potential role of Nup62 in targeting gamma-tubulin and SAS-6 to the centrioles.
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Diagnostic value of distinguishing and reporting different perinuclear ANCA (P-ANCA) immunofluorescence patterns: a prospective study.
Am. J. Clin. Pathol.
PUBLISHED: 07-31-2013
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To investigate whether discriminating the classic perinuclear antineutrophil cytoplasmic antibody (P-ANCA) pattern from atypical P-ANCA and uninterpretable patterns improves the diagnostic utility of ANCA testing.
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A novel tumor: Specimen index for assessing adequacy of resection in early stage oral tongue cancer.
Oral Oncol.
PUBLISHED: 07-19-2013
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Surgical margin status frequently affects decisions regarding adjuvant treatment; however, reporting and interpretation of surgical margins is subject to considerable subjectivity because of many factors including the adequacy of resection. We developed a novel measure of the adequacy of surgical resection, the tumor: specimen index (TSI), and tested its utility at predicting clinical outcomes in a retrospective cohort study.
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Cyclospora infection in a young woman with human immunodeficiency virus in Hong Kong: a case report.
BMC Res Notes
PUBLISHED: 07-04-2013
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Cyclospora is an uncommon pathogen. The diagnosis of Cyclospora infection can be difficult because of its scarcity in developed countries, intracellular mode of life, small size of the parasite and its inability to take up routine microscopic stains. However, it is endemic in many countries in Asia, Africa, Central and South America. With the increase in travels to these areas, the number of cases is expected to increase. Moreover, it is found to be associated with numerous food-borne outbreaks.
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Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-04-2013
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Nucleoporin Nup98 is a component of the nuclear pore complex, and is important in transport across the nuclear pore. Many studies implicate nucleoporin in cancer progression, but no direct mechanistic studies of its effect in cancer have been reported. We show here that Nup98 specifically regulates nucleus-cytoplasm transport of galectin-3, which is a ß-galactoside-binding protein that affects adhesion, migration, and cancer progression, and controls cell growth through the ß-catenin signaling pathway in cancer cells. Nup98 interacted with galectin-3 on the nuclear membrane, and promoted galectin-3 cytoplasmic translocation whereas other nucleoporins did not show these functions. Inversely, silencing of Nup98 expression by siRNA technique localized galectin-3 to the nucleus and retarded cell growth, which was rescued by Nup98 transfection. In addition, Nup98 RNA interference significantly suppressed downstream mRNA expression in the ß-catenin pathway, such as cyclin D1 and FRA-1, while nuclear galectin-3 binds to ß-catenin to inhibit transcriptional activity. Reduced expression of ß-catenin target genes is consistent with the Nup98 reduction and the galectin-3-nucleus translocation rate. Overall, the results show Nup98s involvement in nuclear-cytoplasm translocation of galectin-3 and ß-catenin signaling pathway in regulating cell proliferation, and the results depicted here suggest a novel therapeutic target/modality for cancers.
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A phase 1 study of everolimus + weekly cisplatin + intensity modulated radiation therapy in head-and-neck cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-01-2013
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Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation.
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Oncolytic vaccinia virus therapy of salivary gland carcinoma.
JAMA Otolaryngol Head Neck Surg
PUBLISHED: 02-23-2013
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To examine the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68) against a panel of 5 human salivary gland carcinoma cell lines.
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Endoscopic needle-knife therapy for ileal pouch sinus: a novel approach for the surgical adverse event (with video).
Gastrointest. Endosc.
PUBLISHED: 02-07-2013
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Pouch sinus is an adverse event in patients undergoing ileal pouch surgery.
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High-dose-rate intraoperative brachytherapy and radical surgical resection in the management of recurrent head-and-neck cancer.
Brachytherapy
PUBLISHED: 01-11-2013
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To report long-term outcomes of high-dose-rate (HDR) intraoperative radiotherapy (IORT) at the time of radical resection for recurrent head-and-neck cancer and determine potential prognostic factors.
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Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer.
Int. J. Cancer
PUBLISHED: 01-09-2013
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Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT-based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity-modulated radiation therapy and concurrent chemotherapy underwent post-treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with
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Utility of a histone deacetylase inhibitor (PXD101) for thyroid cancer treatment.
PLoS ONE
PUBLISHED: 01-01-2013
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We evaluated the therapeutic effects of the histone deacetylase inhibitor PXD101 alone and in combination with conventional chemotherapy in treating thyroid cancer.
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Standards and reference materials for the anticardiolipin and anti-?2glycoprotein I assays: a report of recommendations from the APL Task Force at the 13th International Congress on Antiphospholipid Antibodies.
Clin. Chim. Acta
PUBLISHED: 09-15-2011
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The confirmation of diagnosis of the Antiphospholipid Syndrome (APS) relies on laboratory tests. Current classification criteria for definite APS mandate the use of three "standardized" laboratory assays to detect antiphospholipid antibodies (aPL) [viz: anticardiolipin (aCL) IgG and IgM, anti-?(2)glycoprotein I (anti-?(2)GPI) antibodies IgG and IgM and/or a lupus anticoagulant (LAC)], when at least one of the two major clinical manifestations (thrombosis or pregnancy losses) are present. Several attempts have been made to standardize the aCL and anti-?(2)GPI tests, though, a considerable degree of inconsistencies still exist, limiting the clinical and diagnostic value of aPL tests. Among the areas of concern are the type and source of calibrant material, the lack of proper validated reference material and of universal units of measurement, particularly for anti-?(2)GPI antibodies.
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New diagnostic imaging technologies in nonvariceal upper gastrointestinal bleeding.
Gastrointest. Endosc. Clin. N. Am.
PUBLISHED: 08-17-2011
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This article covers new endoscopic imaging modalities in nonvariceal upper gastrointestinal bleeding, such as Doppler ultrasound probe technology, endoscopic ultrasonography, color Doppler optical coherence tomography, and magnification endoscopy. A more in-depth discussion of these modalities and the published evidence supporting their use are included. Furthermore, the shift in focus from identification of conventional visual surface stigmata of recent hemorrhage to an assessment and understanding of subsurface blood flow as it relates to the bleeding lesion is discussed.
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Effective oncolytic vaccinia therapy for human sarcomas.
J. Surg. Res.
PUBLISHED: 08-12-2011
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Approximately one fourth of bone and soft-tissue sarcomas recur after prior treatment. GLV-1h68 is a recombinant, replication-competent vaccinia virus that has been shown to have oncolytic effects against many human cancer types. We sought to determine whether GLV-1h68 could selectively target and lyse a panel of human bone and soft-tissue sarcoma cell lines in vitro and in vivo.
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Visualizing and quantifying acute inflammation using ICAM-1 specific nanoparticles and MRI quantitative susceptibility mapping.
Ann Biomed Eng
PUBLISHED: 08-11-2011
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As intense and prolonged inflammation correlates with the progression of various inflammatory diseases, locating specific regions of the body with dysregulated levels of inflammation could provide crucial information for effective medical diagnosis and treatment. In this study, we demonstrate high resolution spatiotemporal imaging of inflammation in mice treated with systemic injection of lipopolysaccharides (LPS) to mimic systemic inflammatory response or sepsis. Diagnosis of organ-level inflammation was achieved by magnetic resonance imaging (MRI) of inflammation-sensitive superparamagnetic iron oxide (SPIO)-based nanomicelle termed leukocyte-mimetic nanoparticle (LMN), designed to preferentially localize to cells with inflammation-induced overexpression of intercellular adhesion molecule (ICAM)-1. Using a novel MRI quantitative susceptibility mapping (QSM) technique for non-invasive quantification of SPIO nanoparticles, we observed greater accumulation of LMN in the liver, specific to ICAM-1 induction due to LPS-induced inflammation. However, the accumulation of nanoparticles into the spleen appeared to be due to an ICAM-1 independent, phagocytic activity, resulting in higher levels of both LMN and control nanoparticles in the spleen of LPS-treated than untreated mice. Overall, the amounts of nanoparticles in liver and spleen estimated by QSM were in a good agreement with the values directly measured by radioactivity, presenting an idea that spatiotemporal mapping of LMN by MRI QSM may provide a reliable, rapid, non-invasive method for identifying organ-specific inflammation not offered by existing diagnostic techniques.
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Gas chromatographic method validation for the analysis of major components in illicit heroin seized in Malaysia.
Sci. Justice
PUBLISHED: 07-01-2011
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Apart from routine analysis of total morphine content required by the criminal justice system, quantification of other major components in illicit heroin has not been considered by the Malaysian enforcement laboratory. In order to quantify various other cutting agents in addition to alkaloids, a gas chromatographic (GC) method was developed to facilitate simultaneous quantification of eight target analytes commonly found in illicit heroin seized in Malaysia within a 12 min run time. The validation results demonstrated high selectivity with the use of an HP Ultra 2 capillary column. Different solvents were studied and methanol:chloroform (1:9) proved best for sample dissolution. The method was repeatable and reproducible. The study ranges covering 50-150% of the preferred concentrations of the eight analytes obtained r(2)>0.9997. Limits of detection up to 6?g/mL were also obtained and the method achieved 99-102% recovery. The capability of the method in heroin profiling was verified using samples from ten case samples.
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cis-(Dimethyl sulfoxide-?O)[N-(3-eth-oxy-2-oxidobenzyl-idene-?O)-2-hy-droxy-benzohydrazidato-?N,O]dioxido-molybdenum(VI).
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 05-20-2011
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The coordination geometry at the Mo(VI) atom in the title compound, [Mo(C(16)H(14)N(2)O(4))O(2)(C(2)H(6)OS)], is distorted octa-hedral. The phenolate O, imino N, oxide O from the enolized carbonyl group and one of the terminal O atoms form the equatorial plane; the axial positions are occupied by the other terminal O atom of the dioxidomolybdenum group and the donor O atom of DMSO. The O=Mo=O angle is 105.31?(6)°. An intra-molecular O-H?N hydrogen bond and weak inter-molecular C-H?O hydrogen bonds are present in the structure.
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Murine model of neuromuscular electrical stimulation on squamous cell carcinoma: potential implications for dysphagia therapy.
Head Neck
PUBLISHED: 05-18-2011
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Dysphagia is a potential consequence of treatment for head and neck cancer. Neuromuscular electrical stimulation (NMES) has evolved as a treatment option, with the goal of improved swallow function in patients with chronic dysphagia. However, the effects of NMES on tumorigenicity are unknown and often confound the initiation of this therapy, potentially limiting its efficacy in treating patients with head and neck cancer.
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Aqua-[N-(3-eth-oxy-2-oxidobenzyl-?O)furan-1-carbohydrazidato-?N,O]dioxido-molybdenum(VI)-4,4-bipyridine (2/1).
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 05-05-2011
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The Mo(VI) atom in the title co-crystal, [Mo(C(14)H(12)N(2)O(4))O(2)(H(2)O)]·0.5C(10)H(8)N(2), is O,N,O-chelated by the deprotonated Schiff base and coordinated by the oxide and water O atoms in an octa-hedral geometry. The five-membered chelate ring is planar (r.m.s. deviation = 0.019?Å), but the six-membered chelate ring is puckered (r.m.s. deviation = 0.108?Å). Two mononuclear mol-ecules are linked across a center of inversion by an O-H(water)?O hydrogen bond; adjacent dinuclear units are linked by an water-4,4-bipyridine O-H?N hydrogen bond, generating a linear chain structure. The 4,4-bipyridine mol-ecule is disordered over two positions in a 1:1 ratio.
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[N-(5-Chloro-2-oxidobenzyl-?O)-2,4-dihy-droxy-benzohydrazidato-?N,O](methanol-?O)dioxidomolybdenum(VI)-4,4-bipyridine (1/1).
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 05-05-2011
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In the title co-crystal, [Mo(C(14)H(9)ClN(2)O(4))O(2)(CH(3)OH)]·C(10)H(8)N(2), the deprotonated Schiff base O,N,O-chelates to the Mo(VI) atom, the three atoms involved in chelation comprising the fac sites of the octa-hedron surrounding the methanol-coordinated metal atom. The methanol mol-ecule forms an O-H?N hydrogen bond to an N atom of the 4,4-bipyridine solvent mol-ecule; the hy-droxy group of the Schiff base forms an O-H?N hydrogen bond to the other N atom of another mol-ecule. The two hydrogen bonds leading to the formation of a helical chain running along the b axis.
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Prevalence and clinical significance of pancreatic cysts associated with cysts in other organs.
Dig Liver Dis
PUBLISHED: 05-02-2011
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Von Hippel-Lindau disease is associated with serous cysts in the pancreas and kidneys. In this study we determined the prevalence of pancreatic cysts occurring concurrently with other abdominal cysts and tested the hypothesis that these patients might represent a forme fruste of Von Hippel-Lindau disease and be more likely to be serous cysts.
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RNA export factor RAE1 contributes to NUP98-HOXA9-mediated leukemogenesis.
Cell Cycle
PUBLISHED: 05-01-2011
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Chromosomal translocations involving chimeric fusions of the nucleoporin NUP98 protein have often been described in acute myelogenous leukemia (AML). All the fusion proteins have an identical NUP98 N terminus, which contains the GLEBS motif for interaction with the mRNA export factor RAE1 and FG repeats that associate with the transcription factors HDAC1 and p300. It is virtually unknown whether these interaction partners affect leukemogenesis. We previously showed that RAE1 depletion caused aneuploidy, which enhanced tumorigenesis. We speculated that RAE1 may also be directly involved in NUP98 fusion-mediated leukemogenesis. We show here that RNA interference (RNAi)-mediated knockdown of NUP98 caused severe chromosome segregation defects and disrupted RAE1 but not HDAC1 expression and localization. Next, we performed rescue experiments to confirm that the RAE1-NUP98 complex orchestrates proper chromosome segregation. Interestingly, we found diverse behaviors of NUP98 and the leukemogenic fusion protein NUP98-HOXA9 throughout the cell cycle. Strikingly, in NUP98-HOXA9-transfected cells, RAE1 protein were reduced and mis-localized. Our cellular interpretations were further confirmed by NUP98-HOXA9 transgenic mice and the NUP98-HOXA9 AML patient. These data suggest that RAE1 orchestrates NUP98-mediated leukemogenesis and raise the possibility that targeting this negative feedback loop may provide a new strategy for the therapy of aggressive leukemias.
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Optimization of Exactive Orbitrap™ acquisition parameters for quantitative bioanalysis.
Bioanalysis
PUBLISHED: 04-23-2011
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Orbitrap™ mass spectrometry has made significant impacts in the qualitative field of mass spectrometry, and it can be a potentially powerful quantitative technique. Because the Orbitrap is a relatively new platform, our understanding of this technology is not as well-versed as other mass spectrometric techniques.
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Inflamed leukocyte-mimetic nanoparticles for molecular imaging of inflammation.
Biomaterials
PUBLISHED: 04-21-2011
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Dysregulated host inflammatory response causes many diseases, including cardiovascular and neurodegenerative diseases, cancer, and sepsis. Sensitive detection of the site of inflammation will, therefore, produce a wide-ranging impact on disease diagnosis and treatment. We hypothesized that nanoprobes designed to mimic the molecular interactions occurring between inflamed leukocytes and endothelium may possess selectivity toward diverse host inflammatory responses. To incorporate inflammation-sensitive molecular interactions, super paramagnetic iron oxide nanoparticles were conjugated with integrin lymphocyte function-associated antigen (LFA)-1 I domain, engineered to mimic activated leukocytes in physiology. Whole body optical and magnetic resonance imaging in vivo revealed that leukocyte-mimetic nanoparticles localized preferentially to the vasculature within and in the invasive front of the tumor, as well as to the site of acute inflammation. This study explored in vivo detection of tumor-associated vasculature with systemically injected inflammation-specific nanoparticles, presenting a possibility of tumor detection by inflamed tumor microenvironment.
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Kimura disease: diagnostic challenges and clinical management.
Am J Otolaryngol
PUBLISHED: 03-25-2011
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Kimura disease is a rare inflammatory lesion of the head and neck region, usually seen in young Asian men. Patients usually present with a painless mass involving a major salivary gland with lymphadenopathy. Current studies suggest an immunologic mechanism for the pathogenesis of this disease entity. Histopathologically, this tumor is composed of vascular proliferation and lymphoid infiltrate rich in eosinophils. The immunohistochemical findings are usually nonspecific but might help in eliminating malignancies. The role of fine needle aspiration (FNA) and biopsy procedure appears to be limited in making the histologic diagnosis of Kimura disease. The natural history of the disease, however, appears to be indolent, without any malignant transformation reported, although recurrence can be frequent. Here, we describe 2 cases of Kimura disease with differing presentations, diagnostic difficulties, and their clinical management. The difficulties encountered in establishing an accurate preoperative diagnosis and the complexity of surgical management highlight the need for an index of suspicion for this clinical entity while mandating appropriate surgical management to minimize operative morbidity and reduce the risk of recurrence.
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Intensity-modulated radiation therapy in oropharyngeal carcinoma: effect of tumor volume on clinical outcomes.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-23-2011
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To analyze the effect of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) on treatment outcomes in patients treated with definitive intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC).
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Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats.
PLoS ONE
PUBLISHED: 03-18-2011
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Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress.
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The role of nuclear pore complex in tumor microenvironment and metastasis.
Cancer Metastasis Rev.
PUBLISHED: 02-08-2011
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One of the main reasons for cancer mortality is caused by the highly invasive behavior of cancer cells, which often due to aggressive metastasis. Metastasis is mediated by various growth factors and cytokines, operating through numerous signaling pathways. Remarkably, all these metastatic signaling pathways must enter the nucleus through a single gatekeeper, the nuclear pore complex (NPC). NPCs are the only gateway between the cytoplasm and the nucleus. NPCs are among the largest proteinaceous assemblies in the cell and are composed of multiple copies of around 30 different proteins called nucleoporins. Here, we review what is currently known about the NPC, and its role in the mechanisms of tumor progression. We will also explore potential strategies to target metastatic pathways by manipulating the karyopherins (importins/exportins) of nucleocytoplasmic traffic through NPCs.
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Combination of pet imaging with viral vectors for identification of cancer metastases.
Adv. Drug Deliv. Rev.
PUBLISHED: 02-06-2011
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There are three main ways for dissemination of solid tumors: direct invasion, lymphatic spread and hematogenic spread. The presence of metastases is the most significant factor in predicting prognosis and therefore evidence of metastases will influence decision-making regarding treatment. Conventional imaging techniques are limited in the evaluation and localization of metastases due to their restricted ability to identify subcentimeter neoplastic disease. Hence, there is a need for an effective noninvasive modality that can accurately identify occult metastases in cancer patients. One such method is the combination of positron emission tomography (PET) with vectors designed for delivery of reporter genes into target cells. Vectors expressing the herpes simplex virus-1 thymidine kinase (HSV1-tk) reporter system have recently been shown to allow localization of micrometastases in animal models of cancer using non invasive imaging. Combination of HSV1-tk and PET imaging is based on the virtues of vectors which can carry and selectively express the HSV1-tk reporter gene in a variety of cancer cells but not in normal tissue. A radioactive tracer which is applied systemically is phosphorylated by the HSV1-tk enzyme, and as a consequence, the tracer accumulates in proportion to the level of HSV1-tk expression which can be imaged by PET. In this paper we review the recent developments in molecular imaging of micrometastases using replication-competent viral or nonviral vectors carrying the HSV1-tk gene using PET imaging. These diagnostic paradigms introduce an advantageous new concept in noninvasive molecular imaging with the potential benefits for improving patient care by providing guidance for therapy to patients with risk for metastases.
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Unexpected role of nucleoporins in coordination of cell cycle progression.
Cell Cycle
PUBLISHED: 02-01-2011
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Many human cancers have irregular chromosome content, a condition known as aneuploidy. Several nuclear pore proteins (nucleoporins/Nups) that mediate transport of RNA or macromolecules into and out of the nucleus have been implicated in mitosis. These nucleoporins are involved in molecular networks that function in a variety of mitotic processes, including chromosome condensation, sister chromatid cohesion, kinetochore assembly and spindle formation. An alteration in the concentration of Nups inside cells often causes aneuploidy. In this review, we discuss this sprouting area and the possible functions of Nups during mitosis.
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Laboratory testing for the antiphospholipid syndrome: making sense of antiphospholipid antibody assays.
Clin. Chem. Lab. Med.
PUBLISHED: 01-31-2011
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The antiphospholipid syndrome (APS) is an autoimmune condition characterised by a wide range of clinical features (primarily thrombosis and/or obstetric related), associated with the presence of antiphospholipid antibodies (aPL) as detected by a diverse range of laboratory tests. APS remains a significant diagnostic challenge for clinicians across a wide range of specialities, largely due to issues related to laboratory testing as well as the expanding range of reported clinical manifestations of APS. The laboratory issues include limitations in detailed knowledge by both clinical and laboratory personnel regarding the complete range of available aPL tests, as well as ongoing problems with assay reproducibility and standardisation. aPL are identified using diverse laboratory procedures based on one of two distinct test processes, namely solid phase and liquid phase assays. The former includes anticardiolipin antibodies (aCL) and anti-?(2)-glycoprotein I antibodies (a?(2)GPI). The latter are centred on clot-based tests that are used to identify the so-called lupus anticoagulant (LA). This article will discuss: (i) issues related to laboratory testing for APS in terms of the currently available solid-phase and liquid-phase assays, and identifiable biases resulting from these tests usually being performed in different laboratories; (ii) current problems with calibration, standardisation and reproducibility of these assays; (iii) pre-analytical, analytical and post-analytical considerations and ongoing initiatives for improvement; (iv) issues related to potential combinations/panels of available aPL tests; and (v) the entities of seropositive APS, seronegative APS and non-APS aPL-positivity. In doing so, this review will hopefully help bridge the two disciplines of haematology and immunology (representing liquid-phase and solid-phase aPL testing, respectively), by improving the understanding of those working in each of these disciplines of the merits and limitations of the assays performed in the other discipline, and encouraging inter-discipline cooperation in the reporting of aPL test results.
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Correlation of osteoradionecrosis and dental events with dosimetric parameters in intensity-modulated radiation therapy for head-and-neck cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-27-2011
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Osteoradionecrosis (ORN) is a known complication of radiation therapy to the head and neck. However, the incidence of this complication with intensity-modulated radiation therapy (IMRT) and dental sequelae with this technique have not been fully elucidated.
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Target volume delineation in oropharyngeal cancer: impact of PET, MRI, and physical examination.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-12-2011
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Sole utilization of computed tomography (CT) scans in gross tumor volume (GTV) delineation for head-and-neck cancers is subject to inaccuracies. This study aims to evaluate contributions of magnetic resonance imaging (MRI), positron emission tomography (PET), and physical examination (PE) to GTV delineation in oropharyngeal cancer (OPC).
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Development of an extemporaneous oral liquid formulation of oxandrolone and its stability evaluation.
Burns
PUBLISHED: 01-10-2011
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Many references exist in the literature identifying the usefulness of oxandrolone in treating muscle wasting due to various conditions including severe burns. However, there is an absence of dosage form alternatives as it is only available as tablets. The dose for children is weight based (0.1 mg/kg) which is difficult to achieve with the currently available tablets of 2.5 mg and 10 mg. The literature provides ample evidence of clinical importance but little guidance on extemporaneous oral liquid formulation of oxandrolone. In order to develop and validate an extemporaneous liquid formulation, suspensions of oxandrolone were developed using locally available (New Zealand) vehicles. Combinations of these vehicles with ethanol, as advised in some articles were also tried. Assay method was developed for oxandrolone using High Performance Liquid Chromatography (HPLC) and Mass Spectroscopy (LC-MS). The formulations were evaluated for stability as per the International Conference on Harmonization (ICH) stability guidelines. They were observed for physical and chemical stability at different time points over a period of 28 days. A stable and validated liquid formulation of oxandrolone has been developed which can be made under the hospital and community pharmacy conditions. The formula utilises commercially available oxandrolone tablets, crushed and dispersed in Simple Syrup BP or Orablend(®) vehicle. The formulation has confirmed stability for 21 days and can be easily made with locally available vehicles.
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Interleukin-15:Interleukin-15 receptor ? scaffold for creation of multivalent targeted immune molecules.
Protein Eng. Des. Sel.
PUBLISHED: 12-21-2010
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Human interleukin-15 (hIL-15) and its receptor ? (hIL-15R?) are co-expressed in antigen presenting cells allowing trans-presentation of the cytokine to immune effector cells. We exploited the high-affinity interactions between hIL-15 and the extracellular hIL-15R? sushi domain (hIL-15R?Su) to create a functional scaffold for the design of multispecific fusion protein complexes. Using single-chain T cell receptors (scTCRs) as recognition domains linked to the IL-15:IL-15R? scaffold, we generated both bivalent and bispecific complexes. In these fusions, the scTCR domains retain the antigen-binding activity and the hIL-15 domain exhibits receptor binding and biological activity. As expected, bivalent scTCR fusions exhibited improved antigen binding due to increased avidity, whereas fusions comprising two different scTCR domains were capable of binding two cognate peptide/MHC complexes. Bispecific molecules containing scTCR and scCD8?? domains also exhibit enhanced binding to peptide/MHC complexes, demonstrating that the IL-15:IL-15R? scaffold displays flexibility necessary to support multi-domain interactions with a given target. Surprisingly, functional heterodimeric molecules could be formed by co-expressing the TCR ? and ? chains separately as fusions to the hIL-15 and hIL-15R?Su domains. Together, these properties indicate that the hIL-15 and hIL-15R?Su domains can be used as versatile, functional scaffold for generating novel targeted immune molecules.
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Total care requirements of burn patients: implications for a disaster management plan.
J Burn Care Res
PUBLISHED: 11-25-2010
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The purpose of this study was to determine the operative and ward-based requirements of burn patients as a first step in the development of a National Health Emergency Multiple Complex Burn Action Plan. A retrospective review of 1043 patients admitted to the National Burn Centre at Middlemore Hospital, Auckland, New Zealand, from June 2006 to June 2009 was undertaken. Outcome measures included the number of operative procedures, operative time, length of inpatient stay, nursing hours, and allied health hours. A mean of 0.3 operating theater visits and 22.8 minutes of operating time was needed per percentage total body surface area (TBSA) burn. Length of inpatient stay equated to 1.1 days per percentage TBSA burn. There was an exponential relationship between operative requirements and burn surface area. Total operating theater time could be predicted from a formula based on burn surface area, mean depth, and type of burn. Operative time required was greatest in the first week and roughly halved each week after this, whereas nursing and allied health hours remained relatively constant. On the basis of operative requirements in the first week, patients with acute burn injuries totaling up to 129% TBSA could be treated at one time at the authors institution. This study provides an objective trigger point for the activation of a disaster plan and enables us to predict operative and staffing requirements on a week by week basis, taking into account the existing workload. This information can be used to plan both the acute and protracted phase of a national response to a burn disaster.
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Probing sepsis and sepsis-like conditions using untargeted SPIO nanoparticles.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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Sepsis is the leading cause of death in critically ill patients in the United States. Current diagnosis of sepsis relies heavily on the patients manifestation of septic symptoms, which occur at life-threatening late stage of sepsis. Because the underlying biological changes of sepsis occur hours to days before the clinical presentation of symptoms, early detection of the biological changes will provide crucial opportunities for early diagnosis and effective treatment of sepsis. As an candidate for early sepsis detection, we propose using a novel quantitative susceptibility mapping (QSM) MRI that quantifiably measure the activity of the immune system during sepsis progression. It has been observed that Kupffer cells, comprising 80% of the livers macrophages, play a pivotal role in the early response to system infection, a condition characteristic of sepsis. Further, it has been observed that phagocytosis by Kupffer cells is a major mechanism by which nanoparticle-based contrast agents, such as Feridex, are cleared from the body. By quantifying the amount of superparamagnetic iron-oxide nanoparticles uptaken by these macrophages and correlating this result to immune system response and the progression of sepsis, we can utilize commonly used contrast agents as markers in monitoring and diagnosing sepsis condition. This study offers an in vitro proof of concept; RAW264.7 murine monocytes were treated with lipopolysaccharide to induce a sepsis-like cell condition, incubated with the FDA-approved contrast agent Feridex IV, and imaged using QSM MRI for the quantification of iron.
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Use and monitoring of low dose rituximab in myasthenia gravis.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 11-11-2010
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Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Rituximab (RTX), a monoclonal antibody to CD20, leads to B lymphocyte depletion and has been used in some autoimmune disorders, including small case series of myasthenia gravis patients.
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Prognostic implication of sentinel lymph node biopsy in cutaneous head and neck melanoma.
Head Neck
PUBLISHED: 09-18-2010
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Current therapy for intermediate thickness melanoma involves wide local excision with sentinel lymph node biopsy (SLNB). SLNB provides important prognostic information and immediate regional lymphadenectomy for a positive sentinel lymph node (SLN) may improve survival and identifies patients who are candidates for adjuvant therapy and/or clinical trials. The head and neck site is unique because of its complex lymphatic drainage pattern to multiple nodal basins and because of the risk of site-specific morbidity associated with regional lymphadenectomy when compared to other body sites. The goal of this study is to report the results of SLNB for head and neck cutaneous melanoma in locating the sentinel node and to report on the prognostic implications of SLNB for this cohort of patients.
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Therapeutic effects of a fusogenic newcastle disease virus in treating head and neck cancer.
Head Neck
PUBLISHED: 08-12-2010
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Newcastle disease virus (NDV) is a paramyxovirus that is pathogenic in birds but causes only mild flulike symptoms in human beings. NDV(F3aa)-GFP is a genetically modified, fusogenic NDV. We assessed the utility of NDV(F3aa)-GFP in treating head and neck squamous cell carcinoma.
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GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase.
Cancer Sci.
PUBLISHED: 07-30-2010
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GI24, an immunoglobulin superfamily member, has been cloned from a placenta cDNA library as a gene product that promoted activation of matrix metalloproteinase (MMP)-2 mediated by membrane type (MT) 1-MMP. Co-expression of GI24 with MT1-MMP in HEK293T cells increased the cell-surface level of MT1-MMP concomitant with the cleavage of the GI24 at the juxtamembrane site to shed the extracellular domain. HT1080 fibrosarcoma cells stably transfected with the GI24 gene expressed a higher level of MT1-MMP and showed more invasive ability in collagen gel than the control cells. GI24 was cleaved in HT1080 cells, which was blocked by the administration of MMP inhibitor BB94 or transfection of small interfering RNA (siRNA) targeting MT1-MMP. GI24 expression is relatively high in some squamous carcinoma and hepatocarcinoma cell lines. Transfection of siRNA for GI24 into oral squamous carcinoma-derived HSC-4 cells, which express GI24 and MT1-MMP genes reduced the expression of not only GI24 but also MT1-MMP, and attenuated invasive growth in the collagen matrix. These results suggest that GI24 contributes to tumor-invasive growth in the collagen matrix by augmenting cell surface MT1-MMP.
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Unambiguous identification of superparamagnetic iron oxide particles through quantitative susceptibility mapping of the nonlinear response to magnetic fields.
Magn Reson Imaging
PUBLISHED: 05-19-2010
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Superparamagnetic iron oxide (SPIO) particles generate signal void regions on gradient echo images due to their strong magnetization. In practice, the signal void region might be indistinguishable from that generated by air. However, the response of SPIO to an externally applied magnetic field is nonlinear. Magnetization of SPIO saturates at around 1 T while magnetization of water and air increase linearly with field strength. Phantom experiment and mice experiments demonstrated the feasibility of a nonambiguous identification of superparamagnetic contrast agents.
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An update on cohesin function as a molecular glue on chromosomes and spindles.
Cell Cycle
PUBLISHED: 05-18-2010
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One of the critical events in mitosis is proper sister chromatid cohesion, which is mediated by a protein complex called cohesin. The cohesin complex is best known for its role in tethering the sister DNA molecules. This review summarizes recent progress in understanding the functions of cohesin, and of its major subunits, SMC1, SMC3, Scc1 and Scc3. It is now clear that cohesin also plays crucial roles in controlling transcription and gene expression, DNA damage repair and spindle pole formation; functions that are beyond the traditional view of cohesin as a molecular glue that holds sister chromosomes together.
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Clinical triage decision vs risk scores in predicting the need for endotherapy in upper gastrointestinal bleeding.
Am J Emerg Med
PUBLISHED: 04-13-2010
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Acute upper gastrointestinal hemorrhage (UGIH) is a common reason for hospitalization with substantial associated morbidity, mortality, and cost. Differentiation of high- and low-risk patients using established risk scoring systems has been advocated. The aim of this study was to determine whether these scoring systems are more accurate than an emergency physicians clinical decision making in predicting the need for endoscopic intervention in acute UGIH.
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Rapid and accurate left ventricular chamber quantification using a novel CMR segmentation algorithm: a clinical validation study.
J Magn Reson Imaging
PUBLISHED: 04-08-2010
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To evaluate the clinical performance of a novel automated left ventricle (LV) segmentation algorithm (LV-METRIC) that involves no geometric assumptions.
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Experience with the new 4-way, 5.5-mm ultrathin endoscope: a case series.
Dig. Dis. Sci.
PUBLISHED: 03-31-2010
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Use of ultrathin (ut) endoscopes is sometimes limited by their design (outer diameter, tip angulation and image quality). New ut-endoscopes are being designed to address these limitations. A new ut-endoscope, XGIF-PV70N5 (Olympus America Inc.), with an outer diameter of 5.5 mm, 4-way angulation and narrow band imaging has recently been introduced. In this study, we report our subjective experience with this prototype ut-endoscope and discuss the practical uses of its new features.
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Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-16-2010
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To compare concurrent cisplatin (CDDP) and radiation (RT) with cetuximab (C225) and RT for locally advanced head-and-neck cancer (LAHNC).
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Variability in measurements of pancreatic cyst size among EUS, CT, and magnetic resonance imaging modalities.
Gastrointest. Endosc.
PUBLISHED: 03-15-2010
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Cyst size is an important factor in the management of pancreatic cysts, both in predicting the need for surgery and the frequency of follow-up.
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Psychosocial functioning among HIV-affected youth and their caregivers in Haiti: implications for family-focused service provision in high HIV burden settings.
AIDS Patient Care STDS
PUBLISHED: 03-11-2010
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The study is an analysis of baseline data from a pilot psychosocial support intervention for HIV-affected youth and their caregivers in Haiti. Six sites in Haitis Central Department affiliated with Partners In Health/Zanmi Lasante (PIH/ZL) and the Haitian Ministry of Health were included. Participants were recruited from a list of HIV-positive patients receiving care at PIH/ZL. The baseline questionnaire was administered from February 2006 to January 2007 with HIV-affected youth (n = 492), ages 10-17, and their caregivers (n = 330). According to findings at baseline, the youth reported high levels of anxiety, including constant fidgeting (86%), restlessness (83%), and worrying a lot (56%). Their parents/caregivers also reported a high level of depressive symptoms, such as low energy (73%), feeling everything is an effort (71%), and sadness (69%). Parents depressive symptoms were positively associated with their childrens psychological symptoms (odds ratio [OR] =1.6-2.4) and psychosocial functioning (OR =1.6 according to parental report). The significant levels of anxiety and depression observed among HIV-affected youth and their caregivers suggest that psychosocial interventions are needed among HIV-affected families in central Haiti and other high HIV burden areas. The results suggest that a family-focused approach to service provision may be beneficial, possibly improving quality of life, as well as psychosocial and physical health-related outcomes among HIV-affected youth and their caregivers, particularly HIV-positive parents.
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Endoscopic Doppler US for the prevention of ulcer bleeding after endoscopic submucosal dissection for early gastric cancer: a preliminary study (with video).
Gastrointest. Endosc.
PUBLISHED: 02-22-2010
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After endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), delayed bleeding occurs in 1.7% to 38% of cases. Routine coagulation of all nonbleeding visible vessels (NBVVs) in post-ESD ulcers is currently performed as standard practice, but it cannot eliminate bleeding. An endoscopic Doppler US (DOP-US) probe system has possible benefits for the prediction of recurrent bleeding in peptic ulcer hemorrhage.
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The role of the head and neck surgeon in contemporary multidisciplinary treatment programs for advanced head and neck cancer.
Curr Opin Otolaryngol Head Neck Surg
PUBLISHED: 02-20-2010
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The advent of contemporary multidisciplinary treatment programs for head and neck cancer has led to a shift away from primary surgery for advanced pharyngeal and laryngeal carcinomas, in favor of concurrent chemoradiation therapy. Although primary surgical resection may no longer be the most commonly selected initial therapy for these patients, the head and neck surgeon should remain a key participant in their multidisciplinary care. We review the various ways in which the head and neck surgeon contributes to the care of these patients.
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Oncolysis using herpes simplex virus type 1 engineered to express cytosine deaminase and a fusogenic glycoprotein for head and neck squamous cell carcinoma.
Arch. Otolaryngol. Head Neck Surg.
PUBLISHED: 02-17-2010
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To determine if prodrug conversion of fluorocytosine to fluorouracil by an engineered herpes virus, OncoVEX(GALV/CD), enhances oncolytic therapy of head and neck squamous cell carcinoma.
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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.

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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.