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Find video protocols related to scientific articles indexed in Pubmed.
Gefitinib induces cytoplasmic translocation of the CDK inhibitor p27 and its binding to a cleaved intermediate of caspase 8 in non-small cell lung cancer cells.
Cell Oncol (Dordr)
PUBLISHED: 09-03-2014
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The epidermal growth factor receptor (EGFR) represents one of the first rationally selected molecules for targeted therapy in non-small cell lung cancer (NSCLC). Gefitinib is a reversible and highly selective tyrosine kinase inhibitor that competitively blocks the binding of adenosine triphosphate to its binding site in the tyrosine kinase domain of the EGFR. It has been found that treatment with gefitinib induces cell cycle arrest and apoptosis in NSCLC cells harboring activating EGFR mutations. Despite its clinical relevance, however, the mechanism underlying gefitinib-induced apoptosis has remained largely unknown.
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Metabolic engineering of Corynebacterium glutamicum for the production of L-ornithine.
Biotechnol. Bioeng.
PUBLISHED: 08-28-2014
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L-ornithine is a non-essential amino acid for various industrial applications in food industry. In this study, Corynebacterium glutamicum ATCC 13032 was metabolically engineered for the production of L-ornithine. First, the proB and argF genes were deleted to block the competitive branch pathway and to block the conversion of L-ornithine to citrulline, respectively. In addition, the argR gene encoding the regulatory repressor of the L-arginine operon was also deleted. The resulting strain produced 230?mg/L of L-ornithine from glucose in flask culture. This base strain was further engineered by the plasmid-based overexpression of the argCJBD genes from C. glutamicum ATCC 21831, which resulted in the production of 7.19?g/L of L-ornithine. To enrich the NADPH pool, the carbon flux was redirected towards the pentose phosphate pathway by changing the start codons of the pgi and zwf genes and replacing the native promoter of the tkt operon with the strong sod promoter. Fed-batch cultivation of this final strain YW06 (pSY223) allowed production of 51.5?g/L of L-ornithine in 40?h with the overall productivity of 1.29?g/L/h. The results obtained in this study demonstrate the possibility of efficiently producing L-ornithine by metabolically engineered C. glutamicum. Biotechnol. Bioeng. 2014;9999: 1-6. © 2014 Wiley Periodicals, Inc.
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The Combination of irreversible EGFR TKIs and SAHA induces apoptosis and autophagy-mediated cell death to overcome acquired resistance in EGFR T790M-mutated lung cancer.
Int. J. Cancer
PUBLISHED: 05-09-2014
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To overcome T790M-mediated acquired resistance of lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), second generation TKIs such as BIBW2992 (afatinib) and third generation TKIs including WZ4002 have been developed. However, clinical data on their efficacy in treating T790M mutant tumors are lacking. Histone deacetylase (HDAC) inhibitors have been reported to arrest cell growth and to lead to differentiation and apoptosis of various cancer cells, both in vitro and in vivo. In the present study, we assessed whether the combination of suberoylanilide hydroxamic acid (SAHA, vorinostat), a potent HDAC inhibitor, and BIBW2992 or WZ4002 could overcome EGFR TKI resistance associated with T790M mutation in lung cancer cells. While treatment with BIBW2992 or WZ4002 alone slightly reduced the viability of PC-9G and H1975 cells, which possess T790M mutation, combining them with SAHA resulted in significantly decreased cell viability through the activation of the apoptotic pathway. This combination also enhanced autophagy occurrence and inhibition of autophagy significantly reduced the apoptosis induced by the combination treatment, showing that autophagy is required for the enhanced apoptosis. Caspase-independent autophagic cell death was also induced by the combination treatment with SAHA and either BIBW2992 or WZ4002. Finally, the combined treatment with SAHA and either BIBW2992 or WZ4002 showed an enhanced anti-tumor effect on xenografts of H1975 cells in vivo. In conclusion, the combination of new generation EGFR TKIs and SAHA may be a new strategy to overcome the acquired resistance to EGFR TKIs in T790M mutant lung cancer. © 2014 Wiley Periodicals, Inc.
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Treatment response and adverse reactions in older tuberculosis patients with immunocompromising comorbidities.
Yonsei Med. J.
PUBLISHED: 08-07-2013
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The aim of this study was to elucidate the effects of immunocompromising comorbidities on treatment response and adverse reactions in older tuberculosis (TB) patients.
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A case of recurrent pulmonary inflammatory myofibroblastic tumor with aggressive metastasis after complete resection.
Tuberc Respir Dis (Seoul)
PUBLISHED: 06-18-2013
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An inflammatory myofibroblastic tumor (IMT) is a rare disease entity reported to arise in various organs. It is thought to be a neoplastic or reactive inflammatory condition, controversially. The treatment of choice for myofibroblastic tumor is surgery, and recurrence is known to be rare. The optimal treatment method is not well-known for patients ineligible for surgery. We report a 47-year-old patient with aggressive recurrent IMT of the lungs. The patient had been admitted for an evaluation of back-pain two years after a complete resection of pulmonary IMT. Radiation therapy was performed for multiple bone recurrences, and the symptoms were improved. However the patient presented again with aggravated back-pain six months later. High-dose steroid and non-steroidal anti-inflammatory drugs were administered, but the disease progressed aggressively, resulting in spinal cord compression and metastasis to intra-abdominal organs. This is a very rare case of aggressively recurrent pulmonary IMT with multi-organ metastasis.
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Autophagy Inhibition with Monensin Enhances Cell Cycle Arrest and Apoptosis Induced by mTOR or Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cells.
Tuberc Respir Dis (Seoul)
PUBLISHED: 03-20-2013
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In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells.
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Clinical effects of gemifloxacin on the delay of tuberculosis treatment.
J. Korean Med. Sci.
PUBLISHED: 01-11-2013
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Although gemifloxacin has low in vitro activity against Mycobacterium tuberculosis, the effect of gemifloxacin on the delay of tuberculosis (TB) treatment has not been validated in a clinical setting. The study group included patients with culture-confirmed pulmonary TB who initially received gemifloxacin for suspected community-acquired pneumonia (CAP). Two control groups contained patients treated with other fluoroquinolones or nonfluoroquinolone antibiotics. Sixteen cases were treated with gemifloxacin for suspected CAP before TB diagnosis. Sixteen and 32 patients were treated with other fluoroquinolones and nonfluoroquinolones, respectively. The median period from the initiation of antibiotics to the administration of anti-TB medication was nine days in the gemifloxacin group, which was significantly different from the other fluoroquinolones group (35 days). The median times for the nonfluoroquinolone group and the gemifloxacin group were not significantly different. There were no significant differences between the gemifloxacin and other fluoroquinolone group in terms of symptomatic and radiographic improvements. However, the frequency of radiographic improvement in the other fluoroquinolones group tended to be higher than in the gemifloxacin group. Gemifloxacin might be the preferred fluoroquinolone for treating CAP, to alleviate any concerns about delaying TB treatment.
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Propylthiouracil-induced nonspecific interstitial pneumonia.
Chest
PUBLISHED: 03-03-2011
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Propylthiouracil (PTU) is a drug used to treat hyperthyroidism. A number of adverse effects have been reported with this drug, including fever, agranulocytosis, skin rash, and vasculitis. PTU-induced interstitial pneumonia is rare--only three cases have been reported--and PTU-induced nonspecific interstitial pneumonia (NSIP) has not been reported. We report a patient who developed NSIP after taking PTU for 1 year. She developed dyspnea, cough, and mild fever lasting 1 month, and a chest CT scan showed multifocal patchy consolidation in both lungs. She underwent a surgical lung biopsy, and NSIP was confirmed pathologically. The symptoms and abnormalities seen in the chest radiograph improved after withdrawal of PTU. To our knowledge, this is the first documented case of pathologically proven PTU-induced NSIP.
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Incidence and risk factors of steroid-induced diabetes in patients with respiratory disease.
J. Korean Med. Sci.
PUBLISHED: 01-24-2011
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Glucocorticoids are effective for treating several respiratory diseases. However, they can cause hyperglycemia. This study determined the incidence and risk factors of steroid-induced diabetes mellitus (S-DM) in patients treated with glucocorticoid for respiratory diseases. A retrospective study examined patients with respiratory diseases treated with a prednisolone-equivalent glucocorticoid dose exceeding 20 mg/day for at least 4 weeks between January 2003 and December 2008. Patients whose initial random glucose level exceeded 200 mg/dL or who had pre-existing diabetes were excluded. S-DM was defined as a fasting glucose concentration exceeding 126 mg/dL or a random glucose concentration exceeding 200 mg/dL at least twice after beginning steroid treatment. A total of 231 patients with respiratory diseases met the inclusion criteria. Their median age was 55 yr, and 139 were female. The median cumulative prednisolone-equivalent glucocorticoid dose was 4,965 mg, and the median duration of steroid treatment was 193 days. S-DM was diagnosed in 34 (14.7%) of 231 patients. Multivariate logistic regression identified older age (odds ratio 1.05, 95% confidence interval 1.02-1.09) as a risk factor for S-DM. S-DM is frequent among patients with respiratory diseases treated with glucocorticoid. Clinicians should be aware of the possibility of S-DM, especially among elderly patients.
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Crystal structure of Rab6A(Q72L) mutant reveals unexpected GDP/Mg²? binding with opened GTP-binding domain.
Biochem. Biophys. Res. Commun.
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The Ras small G protein-superfamily is a family of GTP hydrolases whose activity is regulated by GTP/GDP binding states. Rab6A, a member of the Ras superfamily, is involved in the regulation of vesicle trafficking, which is critical for endocytosis, biosynthesis, secretion, cell differentiation and cell growth. Rab6A exists in two isoforms, termed RabA and Rab6A. Substitution of Gln72 to Leu72 (Q72L) at Rab6 family blocks GTP hydrolysis activity and this mutation usually causes the Rab6 protein to be constitutively in an active form. Here, we report the crystal structure of the human Rab6A(Q72L) mutant form at 1.9Å resolution. Unexpectedly, we found that Rab6A(Q72L) possesses GDP/Mg(2+) in the GTP binding pockets, which is formed by a flexible switch I and switch II. Large conformational changes were also detected in the switch I and switch II regions. Our structure revealed that the non-hydrolysable, constitutively active form of Rab6A can accommodate GDP/Mg(2+) in the open conformation.
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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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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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.