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Find video protocols related to scientific articles indexed in Pubmed.
Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations.
Cancer Discov
PUBLISHED: 07-29-2014
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EGFR-mutant lung cancers responsive to reversible EGFR inhibitors (gefitinib/erlotinib) develop acquired resistance, mediated by second-site EGFR T790M mutation in >50% of cases. Preclinically, afatinib (irreversible ErbB family blocker) plus cetuximab (anti-EGFR monoclonal antibody) overcomes T790M-mediated resistance. This phase Ib study combining afatinib and cetuximab enrolled heavily pretreated patients with advanced EGFR-mutant lung cancer and acquired resistance to erlotinib/gefitinib. Patients provided post-acquired-resistance tumor samples for profiling EGFR mutations. Among 126 patients, objective response rate (overall 29%) was comparable in T790M-positive and T790M-negative tumors (32% vs. 25%; P = 0.341). Median progression-free survival was 4.7 months (95% confidence interval, 4.3-6.4), and the median duration of confirmed objective response was 5.7 months (range, 1.8-24.4). Therapy-related grade 3/4 adverse events occurred in 44%/2% of patients. Afatinib-cetuximab demonstrated robust clinical activity and a manageable safety profile in EGFR-mutant lung cancers with acquired resistance to gefitinib or erlotinib, both with and without T790M mutations, warranting further investigation.
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Esophageal Reinforcement with an Extracellular Scaffold During Total Gastrectomy for Gastric Cancer.
Ann. Surg. Oncol.
PUBLISHED: 07-20-2014
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Esophagojejunal (EJ) anastomotic leaks after total gastrectomy (TG) for malignancy lead to significant morbidity and mortality, thus affecting long-term survival. Preclinical and clinical trials have shown promise in utilizing degradable extracellular matrix (ECM) scaffolds in buttressing anastomoses. We describe our experience buttressing the EJ anastomosis after TG with a ECM scaffold.
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CD44 expression denotes a subpopulation of gastric cancer cells in which Hedgehog signaling promotes chemotherapy resistance.
Clin. Cancer Res.
PUBLISHED: 06-19-2014
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Gastric cancers may harbor a subset of cells with cancer stem cell (CSC) properties, including chemotherapy resistance, and CD44 is a gastric CSC marker. The Hedgehog (HH) pathway is a key developmental pathway that can be subverted by CSCs during tumorigenesis. Here, we examine the role of HH signaling in CD44(+) gastric cancer cells.
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HER2 directed therapy for gastric/esophageal cancers.
Curr Treat Options Oncol
PUBLISHED: 05-10-2014
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The majority of patients with esophagogastric cancer present with advanced disease, which is incurable. Systemic chemotherapy can lead to a decrease in cancer-related symptoms and prolongs survival. However, even with treatment, the prognosis remains poor; most patients with advanced disease have a median overall survival less than one year. Molecularly targeted therapies, such as those targeting human epidermal growth factor receptor 2 (HER2), are anticipated to improve the current status of systemic treatment beyond conventional cytotoxic therapy. Trastuzumab in combination with chemotherapy in patients is the first molecular agent in metastatic HER2 positive gastric and gastroesophageal adenocarcinomas to result in improvements in response rates, time to progression and survival. Trastuzumab is now being investigated in the neoadjuvant and adjuvant setting. Unfortunately, as with breast cancer, many esophagogastric patients will develop resistance to trastuzumab. Several promising therapies are currently under investigation as monotherapy and in combination with chemotherapy in the first and second line setting.
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Heat shock protein 90 inhibitors in the treatment of cancer: current status and future directions.
Expert Opin Investig Drugs
PUBLISHED: 03-26-2014
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Heat shock protein 90 (HSP90) serves as a critical facilitator for oncogene addiction. There has been augmenting enthusiasm in pursuing HSP90 as an anticancer strategy. In fact, since the initial serendipitous discovery that geldanamycin (GM) inhibits HSP90, the field has rapidly moved from proof-of-concept clinical studies with GM derivatives to novel second-generation inhibitors.
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Prognostic Significance of Targetable Angiogenic and Growth Factors in Patients Undergoing Resection for Gastric and Gastroesophageal Junction Cancers.
Ann. Surg. Oncol.
PUBLISHED: 07-24-2013
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Circulating factors in patients with gastric/gastroesophageal junction (GEJ) cancers may promote tumor progression and metastasis and may be targeted for therapy.
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A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors.
Breast Cancer Res.
PUBLISHED: 05-16-2013
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Trastuzumab is effective in human epidermal growth factor receptor 2 (HER2)-over-expressing breast and gastric cancers. However, patients may develop resistance through downstream signaling via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. This phase 1 trial was conducted to determine the safety and tolerability of the investigational AKT inhibitor MK-2206, to prepare for future studies to determine whether the combination with trastuzumab could inhibit compensatory signaling.
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Distinguishing benign and life-threatening pneumatosis intestinalis in patients with cancer by CT imaging features.
AJR Am J Roentgenol
PUBLISHED: 04-27-2013
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The purpose of this study is to determine the overall proportion of clinically worrisome and benign pneumatosis intestinalis (PI) occurring in patients with cancer and to evaluate associated risk factors and CT features.
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Monitoring afatinib treatment in HER2-positive gastric cancer with 18F-FDG and 89Zr-trastuzumab PET.
J. Nucl. Med.
PUBLISHED: 04-11-2013
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We evaluated the ability of the PET imaging agent (89)Zr-trastuzumab to delineate HER2-positive gastric cancer and to monitor the pharmacodynamic effects of the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor afatinib.
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Human epidermal growth factor receptor 2 testing in gastroesophageal cancer: correlation between immunohistochemistry and fluorescence in situ hybridization.
Arch. Pathol. Lab. Med.
PUBLISHED: 10-29-2011
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Patients with advanced gastroesophageal cancer have poor survival with current therapy. Human epidermal growth factor receptor 2 (HER2) represents a promising therapeutic target, but the optimal HER2 testing strategy is not yet defined.
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An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions.
Oncologist
PUBLISHED: 09-20-2011
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BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported.
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Maintained sensitivity to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer recurring after adjuvant erlotinib or gefitinib.
Clin. Cancer Res.
PUBLISHED: 08-10-2011
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Given the unprecedented efficacy of EGFR tyrosine kinase inhibitors (TKI) in advanced EGFR-mutant lung cancer, adjuvant TKI therapy is an appealing strategy. However, there are conflicting findings regarding the potential benefit of adjuvant EGFR-TKI in patients with lung cancer harboring EGFR mutations. To better understand these results, we studied the natural history of lung cancers which recurred despite adjuvant TKI.
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Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations.
J Thorac Oncol
PUBLISHED: 06-22-2011
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Patients with stage IV lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown.
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Molecular classification of gastric cancer: a new paradigm.
Clin. Cancer Res.
PUBLISHED: 03-23-2011
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Gastric cancer may be subdivided into 3 distinct subtypes--proximal, diffuse, and distal gastric cancer--based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis.
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MET expression and amplification in patients with localized gastric cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 03-10-2011
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MET, the receptor for hepatocyte growth factor, has been proposed as a therapeutic target in gastric cancer. This study assessed the incidence of MET expression and gene amplification in tumors of Western patients with gastric cancer.
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Phase I/II trial of cetuximab and erlotinib in patients with lung adenocarcinoma and acquired resistance to erlotinib.
Clin. Cancer Res.
PUBLISHED: 01-19-2011
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In patients with epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma, treatment with erlotinib or gefitinib is associated with a 75% radiographic response rate and progression-free survival of approximately 12 months. The most common mechanism of acquired resistance to erlotinib is development of a secondary mutation in EGFR, suggesting that these tumors continue to depend on EGFR signaling. We hypothesized that combined EGFR blockade would overcome acquired resistance to erlotinib in patients with lung adenocarcinoma. To evaluate the toxicity and efficacy of cetuximab and erlotinib in patients with acquired resistance to erlotinib, we conducted this phase I/II clinical trial.
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Efficacy and safety of bevacizumab in active brain metastases from non-small cell lung cancer.
J. Neurooncol.
PUBLISHED: 01-18-2010
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Bevacizumab is effective for the treatment of non-small cell lung cancer (NSCLC). Ongoing trials are exploring the safety of bevacizumab in patients with inactive, previously treated brain metastases. However, bevacizumab safety and efficacy in the treatment of active brain metastases is unknown. Bevacizumab received accelerated FDA approval for progressive glioblastoma, a primary brain tumor, because of high response rates and low incidence of intracranial hemorrhage. We retrospectively identified patients treated with bevacizumab for active (treatment naïve or progressive) central nervous system (CNS) metastases from NSCLC. MRI scans performed at least 6 weeks after initiating bevacizumab were assessed for response. There were six patients, four women and two men with a median age of 60 years (range 59-77) at initiation of bevacizumab. Five patients had progressive CNS metastases despite prior treatment including surgery, radiotherapy, and/or chemotherapy; one patient had treatment-naïve brain metastases. Two patients had leptomeningeal metastases, isolated or coexistent with parenchymal brain metastases in one patient each. Bevacizumab was administered alone to one patient and in combination with various cytotoxic chemotherapies in the others. Toxicity included an asymptomatic (Grade 1) intra-tumoral hemorrhage which occurred in one of three patients receiving concurrent anticoagulation with bevacizumab. There was no recurrent CNS bleeding in two patients with a prior history of such hemorrhage. Best CNS response (RECIST) was partial in two, stable disease in three, and progression in one. Median progression-free survival (PFS) was 7.8 months and median overall survival (OS) was 14.1 months following initiation of bevacizumab. Clinical benefit was also observed in the form of improved symptoms and reduced corticosteroid requirements. Bevacizumab should be used with caution in patients with active CNS metastases pending additional safety data. This series suggests bevacizumab may be safe and effective for progressive brain metastases from NSCLC and deserves further study.
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A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors.
Cancer Chemother. Pharmacol.
PUBLISHED: 04-22-2009
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SJG-136 is a pyrrolobenzodiazepine dimer that forms DNA crosslinks and has demonstrated broad antitumor activity. We undertook this trial to determine the maximum-tolerated dose (MTD), toxicities and pharmacokinetic (PK) profile of SJG-136 in patients with an advanced solid tumor.
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Phase II Trial of Cetuximab Plus Cisplatin and Irinotecan in Patients With Cisplatin and Irinotecan-refractory Metastatic Esophagogastric Cancer.
Am. J. Clin. Oncol.
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INTRODUCTION:: Cetuximab in combination with irinotecan has shown clinically significant activity in patients with irinotecan-refractory colon cancer. We evaluated the efficacy of cetuximab in combination with cisplatin and irinotecan in patients with metastatic esophagogastric cancer refractory to cisplatin and irinotecan. PATIENTS AND METHODS:: Patients with disease progression within 3 months of treatment with prior cisplatin and irinotecan received weekly cetuximab and cisplatin/irinotecan for 2 weeks, followed by a 1-week rest period. The primary endpoint was objective response rate. Secondary endpoints included progression-free and overall survival. RESULTS:: Sixteen patients were enrolled (87% with adenocarcinoma). The median prior exposure to cisplatin/irinotecan was 3.6 months. The addition of cetuximab to cisplatin and irinotecan was well tolerated and there were no unexpected toxicities. One of 16 patients treated on study experienced durable RECIST partial response lasting 10 months. The median progression-free survival was 1.4 months (range, 0.5 to10 mo). CONCLUSIONS:: The addition of cetuximab did not overcome irinotecan resistance in patients with metastatic esophagogastric cancer. Further investigation of this strategy in esophagogastric cancer is not justified. The limited activity observed for cetuximab is consistent with other studies evaluating single-agent cetuximab.
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Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib.
J Thorac Oncol
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EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in patients with stage IV lung cancers. The clinical significance of these mutations in patients with resected stage I-III lung cancers is unclear.
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Genomic dysregulation in gastric tumors.
J Surg Oncol
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Gastric cancer is among the most common human malignancies and the second leading cause of cancer-related death. The different epidemiologic and histopathology of subtypes of gastric cancer are associated with different genomic patterns. Data suggests that gene expression patterns of proximal, distal gastric cancers-intestinal type, and diffuse/signet cell are well separated. This review summarizes the genetic and epigenetic changes thought to drive gastric cancer and the emerging paradigm of gastric cancer as three unique disease subtypes.
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HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation.
Cancer Discov
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EGF receptor (EGFR)-mutant lung cancers eventually become resistant to treatment with EGFR tyrosine kinase inhibitors (TKI). The combination of EGFR-TKI afatinib and anti-EGFR antibody cetuximab can overcome acquired resistance in mouse models and human patients. Because afatinib is also a potent HER2 inhibitor, we investigated the role of HER2 in EGFR-mutant tumor cells. We show in vitro and in vivo that afatinib plus cetuximab significantly inhibits HER2 phosphorylation. HER2 overexpression or knockdown confers resistance or sensitivity, respectively, in all studied cell line models. FISH analysis revealed that HER2 was amplified in 12% of tumors with acquired resistance versus only 1% of untreated lung adenocarcinomas. Notably, HER2 amplification and EGFR(T790M) were mutually exclusive. Collectively, these results reveal a previously unrecognized mechanism of resistance to EGFR-TKIs and provide a rationale to assess the status and possibly target HER2 in EGFR-mutant tumors with acquired resistance to EGFR-TKIs.
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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.