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Find video protocols related to scientific articles indexed in Pubmed.
National Working Group Meeting on ALK diagnostics in lung cancer.
Asia Pac J Clin Oncol
PUBLISHED: 02-13-2014
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The global landscape of molecular testing is rapidly changing, with the recent publication of the International Association for the Study of Lung Cancer (IASLC)/College of American Pathologists (CAP) guidelines and the ALK Atlas. The IASLC/CAP guidelines recommend that tumors from patients with non-small cell lung cancer (NSCLC) be tested for ALK rearrangements in addition to epidermal growth factor receptor (EGFR) mutations. The spur for this recommendation is the availability of novel therapies that target these rearrangements. This article is based on coverage of a Pfizer-sponsored National Working Group Meeting on ALK Diagnostics in Lung Cancer, held around the 15th World Lung Cancer Conference, in Sydney on October 31, 2013. It is based on the presentations given by the authors at the meeting and the discussion that ensued. The content for this article was discussed and agreed on by the authors.
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Mucus extravasation into the orbit during frontal sinus irrigation.
Ophthal Plast Reconstr Surg
PUBLISHED: 06-21-2013
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During minitrephination and irrigation of the frontal sinus, mucus extravasated into the orbit through a defect in the sinus floor. The mucus incited a foreign body reaction and became encapsulated within the orbit necessitating excision via an anterior orbitotomy.
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A unique case of pneumatised styloid process with cholesteatoma.
Case Rep Otolaryngol
PUBLISHED: 04-15-2013
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Pneumatisation of styloid process is a very rare finding and has never been reported previously. We present a unique case of a pneumatised styloid process with a cholesteatoma arising within the cavity. We describe the clinical features, associated radiological findings, and management of this lesion.
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Defective lung macrophage function in lung cancer ┬▒ chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?
PLoS ONE
PUBLISHED: 01-01-2013
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In chronic obstructive pulmonary disease (COPD/emphysema) we have shown a reduced ability of lung and alveolar (AM) macrophages to phagocytose apoptotic cells (defective efferocytosis), associated with evidence of secondary cellular necrosis and a resultant inflammatory response in the airway. It is unknown whether this defect is present in cancer (no COPD) and if so, whether this results from soluble mediators produced by cancer cells. We investigated efferocytosis in AM (26 controls, 15 healthy smokers, 37 COPD, 20 COPD+ non small cell lung cancer (NSCLC) and 8 patients with NSCLC without COPD) and tumor and tumor-free lung tissue macrophages (21 NSCLC with/13 without COPD). To investigate the effects of soluble mediators produced by lung cancer cells we then treated AM or U937 macrophages with cancer cell line supernatant and assessed their efferocytosis ability. We qualitatively identified Arachidonic Acid (AA) metabolites in cancer cells by LC-ESI-MSMS, and assessed the effects of COX inhibition (using indomethacin) on efferocytosis. Decreased efferocytosis was noted in all cancer/COPD groups in all compartments. Conditioned media from cancer cell cultures decreased the efferocytosis ability of both AM and U937 macrophages with the most pronounced effects occurring with supernatant from SCLC (an aggressive lung cancer type). AA metabolites identified in cancer cells included PGE2. The inhibitory effect of PGE2 on efferocytosis, and the involvement of the COX-2 pathway were shown. Efferocytosis is decreased in COPD/emphysema and lung cancer; the latter at least partially a result of inhibition by soluble mediators produced by cancer cells that include PGE2.
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Drug targeting to monocytes and macrophages using esterase-sensitive chemical motifs.
J. Pharmacol. Exp. Ther.
PUBLISHED: 07-21-2011
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The therapeutic and toxic effects of drugs are often generated through effects on distinct cell types in the body. Selective delivery of drugs to specific cells or cell lineages would, therefore, have major advantages, in particular, the potential to significantly improve the therapeutic window of an agent. Cells of the monocyte-macrophage lineage represent an important target for many therapeutic agents because of their central involvement in a wide range of diseases including inflammation, cancer, atherosclerosis, and diabetes. We have developed a versatile chemistry platform that is designed to enhance the potency and delivery of small-molecule drugs to intracellular molecular targets. One facet of the technology involves the selective delivery of drugs to cells of the monocyte-macrophage lineage, using the intracellular carboxylesterase, human carboxylesterase-1 (hCE-1), which is expressed predominantly in these cells. Here, we demonstrate selective delivery of many types of intracellularly targeted small molecules to monocytes and macrophages by attaching a small esterase-sensitive chemical motif (ESM) that is selectively hydrolyzed within these cells to a charged, pharmacologically active drug. ESM versions of histone deacetylase (HDAC) inhibitors, for example, are extremely potent anticytokine and antiarthritic agents with a wider therapeutic window than conventional HDAC inhibitors. In human blood, effects on monocytes (hCE-1-positive) are seen at concentrations 1000-fold lower than those that affect other cell types (hCE-1-negative). Chemical conjugates of this type, by limiting effects on other cells, could find widespread applicability in the treatment of human diseases where monocyte-macrophages play a key role in disease pathology.
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Expression profile of the sphingosine kinase signalling system in the lung of patients with chronic obstructive pulmonary disease.
Life Sci.
PUBLISHED: 02-14-2011
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Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Despite its importance, treatment methods are limited and restricted to symptomatic care, highlighting the urgent need for new treatment options. Tissue damage in COPD is thought to result from an inability of the normal repair processes with accumulation of apoptotic material and impaired clearance of this material by macrophages in the airways. Lung inflammation involves the bioactive sphingolipid sphingosine 1-phosphate (S1P).
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Skull base presentation of multiple myeloma.
Ear Nose Throat J
PUBLISHED: 01-14-2011
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Pathologic proliferation of the plasma cell population can produce a wide spectrum of disorders, ranging from benign solitary plasmacytoma to malignant multiple myeloma. The presentation of the resulting disease can be either localized or systemic, depending on the affected area. Multiple myeloma typically presents with systemic symptoms secondary to skeletal lytic lesions, anemia, renal failure, infection, and hyperviscosity syndrome; a diagnosis of multiple myeloma is not suspected in the absence of these features. Multiple myeloma of the skull base is very rare. We present the case of a 66-year-old man who came to us with a 2-year history of disequilibrium and who was found to have multiple myeloma with extensive involvement of the skull base.
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Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a class I selective orally active histone deacetylase inhibitor.
J. Med. Chem.
PUBLISHED: 11-16-2010
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A novel series of HDAC inhibitors demonstrating class I subtype selectivity and good oral bioavailability is described. The compounds are potent enzyme inhibitors (IC?? values less than 100 nM), and improved activity in cell proliferation assays was achieved by modulation of polar surface area (PSA) through the introduction of novel linking groups. Employing oral pharmacokinetic studies in mice, comparing drug levels in spleen to plasma, we selected compounds that were tested for efficacy in human tumor xenograft studies based on their potential to distribute into tumor. One compound, 21r (CHR-3996), showed good oral activity in these models, including dose-related activity in a LoVo xenograft. In addition 21r showed good activity in combination with other anticancer agents in in vitro studies. On the basis of these results, 21r was nominated for clinical development.
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Design and synthesis of novel pyrimidine hydroxamic acid inhibitors of histone deacetylases.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-13-2010
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Inhibition of histone deacetylase activity represents a promising new modality in the treatment of a number of cancers. A novel HDAC series demonstrating inhibitory activity in cell proliferation assays is described. Optimisation based on the introduction of basic amine linkers to effect good drug distribution to tumour led to the identification of a compound with oral activity in a human colon cancer xenograft study associated with increased histone H3 acetylation in tumour tissue.
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Audiovestibular factors influencing quality of life in patients with conservatively managed sporadic vestibular schwannoma.
Otol. Neurotol.
PUBLISHED: 08-05-2010
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To measure the health-related quality of life (QoL) of patients undergoing conservative management of a vestibular schwannoma and to identify audiovestibular factors that influence health-related QoL.
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Hearing improvement in a growing vestibular schwannoma.
Skull Base
PUBLISHED: 09-02-2009
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Vestibular schwannomas are benign, slow-growing tumors that originate from Schwann cells lining the vestibular nerves, most commonly the superior vestibular nerve. They arise at the neurilemmal/neuroglial junction which is situated within the internal auditory canal. They have an incidence of 1 per 100,000 per year and a prevalence of around 700 per million. A case of a patient undergoing a period of observation for a vestibular schwannoma whose hearing improved despite growth of the tumor is described. This raises interesting questions regarding the pathophysiology of hearing loss in patients with vestibular schwannomas. Possible hypotheses are discussed.
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Bruns nystagmus in patients with vestibular schwannoma.
Otol. Neurotol.
PUBLISHED: 05-28-2009
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To determine the prevalence of Bruns nystagmus in patients undergoing surgical treatment for unilateral sporadic vestibular schwannomas (VSs), identify the clinical characteristics of patients with Bruns nystagmus and compare these characteristics with those of VS patients with no nystagmus and other types of nystagmus, and determine the long-term impact of having preoperative Bruns nystagmus.
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Magnetic resonance imaging after translabyrinthine complete excision of vestibular schwannomas.
J Neurol Surg B Skull Base
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The objective of this study is to determine whether magnetic resonance imaging (MRI) at 2 years following complete vestibular schwannoma (VS) excision using a translabyrinthine approach is sufficient to detect recurrent tumor. The study is set in a tertiary referral skull base unit. A service evaluation of a prospective database identified patients who underwent complete translabyrinthine VS excision with prospectively recorded MRI results at 2 and 5 years following surgery. The main outcome measures were evidence of tumor recurrence on MRI at 2 and 5 years after surgery. Of 314 patients in the study, all patients where MRI was reported to show no recurrence at 2 years (97%) also had no signs of recurrence on MRI at 5 years. All eight patients with MRI suspicious of recurrence (linear enhancement of internal auditory canal [IAC]) at 2 years had no progression on MRI at 5 to 15 years. One patient had evidence of definite recurrence (nodular enhancement of IAC) at 2 years, who went on to have radiosurgery at 8 years. Where patients have MRI with no linear enhancement of the IAC at 2 years, no further imaging is required. Where linear enhancement is seen, no change in enhancement at 5 years is reassuring and no further imaging is required.
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Middle fossa repair of bilateral large congenital tegmental defects with meningoencephaloceles.
Ear Nose Throat J
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Spontaneous temporal meningoencephaloceles are unusual. When they do occur, they present with a variety of signs and symptoms, which can make diagnosis and management challenging. We report the interesting case of a 49-year-old woman with bilateral congenital temporal meningoencephaloceles. She presented with a 12-month history of bilateral fluctuating hearing loss, and she more recently developed right-sided acute otitis media with meningitis. The presentation of bilateral extensive tegmental defects and meningoencephaloceles with a fluctuating hearing loss and meningitis associated with acute otitis media affecting one ear and then subsequently the other ear is extremely rare and difficult to diagnose. It requires a very careful clinical and radiologic assessment. Methods of surgical repair differ depending on the size of the defects.
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Growth characteristics of vestibular schwannomas.
Otol. Neurotol.
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To assess the growth characteristics of small- to medium-sized vestibular schwannomas in patients undergoing watch, wait, and rescan management.
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Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer: mechanism for immune evasion?
Lung Cancer
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Cytotoxic CD8(+) T-cells mount immune responses to cancer via cytotoxic pathways including granzyme B. Cancer cells are also known to develop immune evasion mechanisms. We hypothesised that lung cancer cells would over-express the granzyme B-inhibitor, proteinase inhibitor-9 (PI-9) and down-regulate granzyme B expression by neighbouring CD8(+) T-cells. We investigated PI-9 expression in lung cancer cell lines, and primary lung cancer cells obtained at curative lung resection from cancer patients with/without chronic obstructive pulmonary disease (COPD). Granzyme B and PI-9 expression was also determined in CD8(+) T-cells from the cancer and non-cancer areas of resected lung tissue and from bronchoalveolar lavage (BAL). We then evaluated the effects of conditioned media from lung cancer cell lines on granzyme B expression and the cytotoxic activity of CD8(+) T-cells. PI-9 was highly expressed in lung cancer cell lines. Increased PI-9 expression was also observed in primary cancer cells vs. epithelial cells from non-cancer tissue or bronchial brushing-derived normal primary large airway epithelial cells. Expression significantly correlated with cancer stage. Significantly reduced granzyme B was noted in CD8(+) T-cells from cancer vs. non-cancer tissue. Granzyme B production by CD8(+) T-cells was reduced in the presence of conditioned media from lung cancer cell lines. Our data suggest that lung cancer cells utilise their increased PI-9 expression to protect from granzyme B-mediated cytotoxicity as an immune evasion mechanism, a function that increases with lung cancer stage.
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Surgical management of vestibular schwannomas and hearing rehabilitation in neurofibromatosis type 2.
Otol. Neurotol.
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To report our approach to the surgical management of vestibular schwannomas (VSs) and hearing rehabilitation in neurofibromatosis Type 2 (NF2).
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What is Visualize?

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

How does it work?

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

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

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