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Find video protocols related to scientific articles indexed in Pubmed.
AKT regulates NPM dependent ARF localization and p53mut stability in tumors.
Oncotarget
PUBLISHED: 07-30-2014
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Nucleophosmin (NPM) is known to regulate ARF subcellular localization and MDM2 activity in response to oncogenic stress, though the precise mechanism has remained elusive. Here we describe how NPM and ARF associate in the nucleoplasm to form a MDM2 inhibitory complex. We find that oligomerization of NPM drives nucleolar accumulation of ARF. Moreover, the formation of NPM and ARF oligomers antagonizes MDM2 association with the inhibitory complex, leading to activation of MDM2 E3-ligase activity and targeting of p53. We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. We also show that ARF promotes p53 mutant stability in tumors and suppresses p73 mediated p21 expression and senescence. We demonstrate that AKT and PI3K inhibitors may be effective in treatment of therapeutically resistant tumors with elevated AKT and carrying gain of function mutations in p53. Our results show that the clinical candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft model of pancreatic cancer. Analysis of human tumors indicates that phospho-S48-NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of AKT inhibitor treatment. Critically, we propose that combination therapy involving PI3K-AKT inhibitors would benefit from a patient stratification rationale based on ARF and p53(mut) status.
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Targeting mTOR dependency in pancreatic cancer.
Gut
PUBLISHED: 04-09-2014
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Pancreatic cancer is a leading cause of cancer-related death in the Western world. Current chemotherapy regimens have modest survival benefit. Thus, novel, effective therapies are required for treatment of this disease.
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Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel.
BMC Clin Pathol
PUBLISHED: 01-01-2014
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Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.
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Serum amylase on the night of surgery predicts clinically significant pancreatic fistula after pancreaticoduodenectomy.
HPB (Oxford)
PUBLISHED: 07-23-2013
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Drainage after pancreaticoduodenectomy (PD) remains controversial because the risk for uncontrolled postoperative pancreatic fistula (POPF) must be balanced against the potential morbidity associated with prolonged and possibly unnecessary drainage. This study investigated the utility of the level of serum amylase on the night of surgery [postoperative day (PoD) 0 serum amylase] to predict POPF.
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Pre-operative cardiopulmonary exercise testing predicts adverse post-operative events and non-progression to adjuvant therapy after major pancreatic surgery.
HPB (Oxford)
PUBLISHED: 03-06-2013
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BACKGROUND: Surgery followed by chemotherapy is the primary modality of cure for patients with resectable pancreatic cancer but is associated with significant morbidity. The aim of the present study was to evaluate the role of cardiopulmonary exercise testing (CPET) in predicting post-operative adverse events and fitness for chemotherapy after major pancreatic surgery. METHODS: Patients who underwent a pancreaticoduodenectomy or total pancreatectomy for pancreatic head lesions and had undergone pre-operative CPET were included in this retrospective study. Data on patient demographics, comorbidity and results of pre-operative evaluation were collected. Post-operative adverse events, hospital stay and receipt of adjuvant therapy were outcome measures. RESULTS: One hundred patients were included. Patients with an anaerobic threshold less than 10?ml/kg/min had a significantly greater incidence of a post-operative pancreatic fistula [International Study Group for Pancreatic Surgery (ISGPS) Grades A-C, 35.4% versus 16%, P = 0.028] and major intra-abdominal abscesses [Clavien-Dindo (CD) Grades III-V, 22.4% versus 7.8%, P = 0.042] and were less likely to receive adjuvant therapy [hazard ratio (HR) 6.30, 95% confidence interval (CI) 1.25-31.75, P = 0.026]. A low anaerobic threshold was also associated with a prolonged hospital stay (median 20 versus 14 days, P = 0.005) but not with other adverse events. DISCUSSION: CPET predicts a post-operative pancreatic fistula, major intra-abdominal abscesses as well as length of hospital stay after major pancreatic surgery. Patients with a low anaerobic threshold are less likely to receive adjuvant therapy.
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Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater.
J. Clin. Oncol.
PUBLISHED: 02-25-2013
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Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies.
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Activation of the IL-6R/Jak/stat pathway is associated with a poor outcome in resected pancreatic ductal adenocarcinoma.
J. Gastrointest. Surg.
PUBLISHED: 02-08-2013
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Chronic localized pancreatic inflammation in the form of chronic pancreatitis is an established risk factor for human pancreatic ductal adenocarcinoma (PDAC) development. Constitutive activation of inflammation-related signal transducer and activator of transcription (Stat)3 signaling has been implicated in the development and progression a number of malignancies, including PDAC. Although, the Janus Kinase (Jak)/Stat pathway is a potential drug target, clinicopathological, molecular, and prognostic features of Stat3-activated PDAC remain uncertain. Our aim was to determine the clinicopathological impact of this inflammatory pathway in resectable PDAC.
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Step-port laparoscopic cystgastrostomy for the management of organized solid predominant post-acute fluid collections after severe acute pancreatitis.
HPB (Oxford)
PUBLISHED: 01-09-2013
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BACKGROUND: Post-acute pancreatic collections (PAPCs) may require intervention when persistent, large or symptomatic. An open cystgastrostomy is an effective treatment option particularly for larger, solid predominant collections. A laparoscopic cystgastrostomy (LCG) as initially described, could be technically challenging. This report describes the evolution of the operative technique and the results from LCG in a tertiary referral centre. METHODS: Retrospective analysis of the units prospectively populated database was conducted. All patients who underwent a surgical cystgastrostomy (SCG) were identified. Patient demographics, outcome and complications were collected and analysed. RESULTS: Forty-four patients underwent SCG: 8 open and 36 laparoscopic. Of the 36 LCG, 6 required open conversion, although with evolution of the technique all of the last 17 cases were completed laparoscopically. The median interquartile range (IQR) length of stay in patients completed laparoscopically was 6 (2-10) compared with 15.5 days (8-19) in those patients who were converted (P = 0.0351). The only peri-operative complication after a LCG was a self-limiting upper gastrointestinal bleed. With a median (IQR) follow-up of 891 days (527-1495) one patient required re-intervention for a residual collection with no recurrent collections identified. CONCLUSION: LCG is a safe and effective procedure in patients with large, solid predominant PAPCs. With increased experience and technical expertise conversion rates can be lowered and outcome optimized.
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European experts consensus statement on cystic tumours of the pancreas.
Dig Liver Dis
PUBLISHED: 01-08-2013
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Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.
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The prognostic influence of resection margin clearance following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.
J. Gastrointest. Surg.
PUBLISHED: 01-08-2013
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The poor overall survival associated with pancreatic ductal adenocarcinoma (PDAC) despite complete resection suggests that occult metastatic disease is present in most at the time of surgery. Resection margin involvement (R1) following resection is an established poor prognostic factor. However, the definition of an R1 resection varies and the impact of margin clearance on outcome has not been examined in detail.
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MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma.
Clin. Cancer Res.
PUBLISHED: 11-23-2011
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MicroRNAs (miRNA) have potential as diagnostic and prognostic biomarkers and as therapeutic targets in cancer. We sought to establish the relationship between miRNA expression and clinicopathologic parameters, including prognosis, in pancreatic ductal adenocarcinoma (PDAC).
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Clinical potential of microRNAs in pancreatic ductal adenocarcinoma.
Pancreas
PUBLISHED: 10-18-2011
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Aggressive invasion and early metastases are characteristic features of pancreatic ductal adenocarcinoma (PDAC). More than 90% of patients have surgically nonresectable disease at presentation. Despite increasing knowledge of the genetics of this complex disease, systemic therapies, particularly gemcitabine, have modest clinical benefit and marginal survival advantage. MicroRNAs have been shown to have a role in oncogenesis, invasion, and metastases via epigenetic posttranscriptional gene regulation. Our objective was to discuss the clinical impact of microRNAs within PDAC.
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Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression.
Dev. Cell
PUBLISHED: 08-31-2011
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Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation ?5?1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active ?5?1 in late endosomes/lysosomes. CLIC3 is necessary for release of the cell rear during migration on 3D matrices and is required for invasion and maintenance of active Src signaling in organotypic microenvironments. CLIC3 expression predicts lymph node metastasis and poor prognosis in operable cases of pancreatic ductal adenocarcinoma (PDAC). The identification of CLIC3 as a regulator of a recycling pathway and as an independent prognostic indicator in PDAC highlights the importance of active integrin trafficking as a potential drive to cancer progression in vivo.
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Efficacy of an artificial neural network-based approach to endoscopic ultrasound elastography in diagnosis of focal pancreatic masses.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 06-08-2011
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By using strain assessment, real-time endoscopic ultrasound (EUS) elastography provides additional information about a lesions characteristics in the pancreas. We assessed the accuracy of real-time EUS elastography in focal pancreatic lesions using computer-aided diagnosis by artificial neural network analysis.
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Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.
Clin. Cancer Res.
PUBLISHED: 03-28-2011
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The management of pancreatic ductal adenocarcinoma (PDAC) continues to present a great challenge particularly with regard to prediction of outcome following pancreaticoduodenectomy. Molecular markers have been extensively investigated by numerous groups with the aim of enhancing prognostication; however, despite hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the clinical course following resection of PDAC, at this time, no molecular marker assay forms part of recommended clinical practice.
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Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis.
Mol. Cell
PUBLISHED: 01-27-2011
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Mutations in both RAS and the PTEN/PIK3CA/AKT signaling module are found in the same human tumors. PIK3CA and AKT are downstream effectors of RAS, and the selective advantage conferred by mutation of two genes in the same pathway is unclear. Based on a comparative molecular analysis, we show that activated PIK3CA/AKT is a weaker inducer of senescence than is activated RAS. Moreover, concurrent activation of RAS and PIK3CA/AKT impairs RAS-induced senescence. In vivo, bypass of RAS-induced senescence by activated PIK3CA/AKT correlates with accelerated tumorigenesis. Thus, not all oncogenes are equally potent inducers of senescence, and, paradoxically, a weak inducer of senescence (PIK3CA/AKT) can be dominant over a strong inducer of senescence (RAS). For tumor growth, one selective advantage of concurrent mutation of RAS and PTEN/PIK3CA/AKT is suppression of RAS-induced senescence. Evidence is presented that this new understanding can be exploited in rational development and targeted application of prosenescence cancer therapies.
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A prospective comparison of the prognostic value of tumor- and patient-related factors in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 01-26-2011
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Outcome prediction after resection with curative intent for pancreatic ductal adenocarcinoma remains a challenge. There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of common solid tumors. Our aim was to prospectively evaluate the prognostic value of tumor- and patient-related factors including the systemic inflammatory response in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma of the head of pancreas.
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Peripancreatic fat invasion is an independent predictor of poor outcome following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.
J. Gastrointest. Surg.
PUBLISHED: 08-19-2010
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Following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), identification of peripancreatic fat tumor invasion promotes a tumor to stage T3. We sought to understand better the impact of histological peripancreatic fat invasion on prognosis and site of recurrence in a cohort of patients with PDAC.
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Infected pancreatic necrosis: minimizing the cut.
ANZ J Surg
PUBLISHED: 06-26-2010
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The challenge for the pancreatologist managing patients with infected pancreatic necrosis is to devise a treatment algorithm that enables recovery but at the same time limits the morbidity and mortality. The current gold standard remains open necrosectomy. Recent literature contains scattered reports of endoscopic, radiologic, laparoscopic, percutaneous and lumbotomy approaches to managing patients with this condition. This literature review addresses the role of techniques that aim to minimize the physiological insult to the patient with infected pancreatic necrosis.
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Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma.
Ann. Surg.
PUBLISHED: 05-21-2010
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To determine the prognostic influence of residual tumor at or within 1 mm of the mobilization margins (R1Mobilization) compared with transection margins (R1Transection) following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC).
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Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma.
Gastroenterology
PUBLISHED: 02-22-2010
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Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive and metastatic disease for which conventional treatments are of limited efficacy. A number of agents in development are potential anti-invasive and antimetastatic agents, including the Src kinase inhibitor dasatinib. The aim of this study was to assess the importance of Src in human PDAC and to use a genetically engineered mouse model of PDAC to determine the effects of dasatinib on PDAC progression.
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LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest.
Gastroenterology
PUBLISHED: 02-11-2010
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Patients carrying germline mutations of LKB1 have an increased risk of pancreatic cancer; however, it is unclear whether down-regulation of LKB1 is an important event in sporadic pancreatic cancer. In this study, we aimed to investigate the impact of LKB1 down-regulation for pancreatic cancer in mouse and human and to elucidate the mechanism by which Lkb1 deregulation contributes to this disease.
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The relationship between tumor inflammatory cell infiltrate and outcome in patients with pancreatic ductal adenocarcinoma.
Ann. Surg. Oncol.
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The tumor-associated inflammatory cell infiltrate is recognized to have prognostic value in various common solid tumors. However, the prognostic value of the tumor inflammatory cell infiltrate has not been established in pancreatic ductal adenocarcinoma (PDAC) nor has its relationship with the systemic inflammatory response.
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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.

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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.