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Find video protocols related to scientific articles indexed in Pubmed.
Cardiopulmonary Exercise Testing (CPET) as Preoperative Test Before Lung Resection.
In Vivo
PUBLISHED: 11-16-2014
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Lung resection is still the only potentially curative therapy for patients with localized non-small lung cancer (NSCLC). However, the presence of cardiovascular comorbidities and underlying lung disease increases the risk of postoperative complications. Various studies have evaluated the use of different preoperative tests in order to identify patients with an increased risk for postoperative complications, associated with prolonged hospital stay and increased morbidity and mortality. In this topic review, we discuss the role of cardiopulmonary exercise testing (CPET) as one of the preoperative tests suggested for lung cancer patients scheduled for lung resection. We describe different types of exercise testing techniques and present algorithms of preoperative evaluation in lung cancer patients. Overall, patients with maximal oxygen consumption (VO2max) <10 mL/kg/min or those with VO2max <15 mL/kg/min and both postoperative FEV1 and DLCO<40% predicted, are at high risk for perioperative death and postoperative cardiopulmonary complications, and thus should be offered an alternative medical treatment option.
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Soy Allergy Complicating Disease Management in a Child With Coeliac Disease.
Pediatr Allergy Immunol
PUBLISHED: 11-08-2014
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Food allergy is an immune-mediated reaction that occurs reproducibly on exposure to a certain food or food component (most commonly a protein) and is distinct from other conditions causing adverse responses to food, including digestive/absorptive processes, toxic reactions and autoimmune disorders [1]. Coeliac disease (CD) is an autoimmune condition which typically presents with gastrointestinal symptoms and failure to thrive within the first years of life and is caused by an abnormal immunological response to ingested gluten, in genetically predisposed individuals [2,3]. Its diagnosis is primarily based on the presence of characteristic duodenal biopsy findings (villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis) along with documentation of clinical or histological response to a gluten-free diet (GFD) [4]. This article is protected by copyright. All rights reserved.
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8-Isoprostane in exhaled breath condensate of patients with non-small cell lung cancer: the effect of chemotherapy.
Anticancer Res.
PUBLISHED: 09-10-2014
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The aim of the study was to evaluate the exhaled breath condensate (EBC) levels of a valid oxidative stress marker, 8-isoprostane, before and after chemotherapy, in patients with non small cell lung cancer (NSCLC) in correlation with the extent of the disease and response to treatment.
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The intercellular cell adhesion molecule-1 (icam-1) in lung cancer: implications for disease progression and prognosis.
Anticancer Res.
PUBLISHED: 09-10-2014
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The intercellular cell-adhesion molecule-1 (ICAM-1) is a transmembrane molecule and a distinguished member of the Immunoglobulin superfamily of proteins that participates in many important processes, including leukocyte endothelial transmigration, cell signaling, cell-cell interaction, cell polarity and tissue stability. ICAM-1and its soluble part are highly expressed in inflammatory conditions, chronic diseases and a number of malignancies. In the present article we present the implications of ICAM-1 in the progression and prognosis of one of the major global killers of our era: lung cancer.
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Clinical Significance of Smoking Cessation in Patients With Cancer: A 30-Year Review.
Respir Care
PUBLISHED: 09-02-2014
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Despite the established causal relationship between tobacco smoking and cancer, many cancer patients continue to smoke after diagnosis. This partly reflects ignorance of the beneficial effects of smoking cessation, even after diagnosis. The aim of this study was to demonstrate the effects of continuing or quitting smoking in patients with diagnosed cancer.
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DAXAS and COPD Correlation with Cancer.
J Cancer
PUBLISHED: 08-01-2014
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A new drug for chronic obstructive pulmonary disease has been recently added as a treatment for certain patients. However, new evidences indicate that there might be a connection with lung cancer. It is known that smoking is a major factor that induces chronic pulmonary disease and smoking is associated with lung cancer. The level of connection between phosphodiesterase (PDE)-4 inhibitors and lung cancer will be discussed based on current studies. A comment will be made whether lung cancer is induced to patients receiving phosphodiesterase (PDE)-4 inhibitors from the drug or former smoking habit.
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Pharmacogenetics in pancreatic cancer.
JOP
PUBLISHED: 07-31-2014
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Pancreatic cancer is an aggressive malignancy with a poor overall survival rate. Given advances in pharmacogenomics, numerous gene mutations have been identified that could be potential targets for drug development. Therefore, future research strategies may identify prognostic and predictive markers aiming to improve outcome by maximizing efficacy whilst lowering toxicity. In this commentary, we summarize several interesting results regarding pancreatic cancer pharmacogenetics that have been presented in the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. In particular, we focus on Abstract #4124, which investigated the potential predictive role of human equilibrative nucleoside transporter 1 (hENT1) in patients treated with adjuvant gemcitabine for pancreatic cancer, on Abstract #4125, which examined the tolerability of a modified FOLFORINOX study based on UGT1A1*28 genotype guided dosing of IRI in patients with advanced pancreatic cancer, and on Abstract #4130, which confirmed the predictive role of circulating tumor and invasive cells (CTICs) from patients with unresectable pancreatic cancer in second-line chemotherapy treatment setting.
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Risk determination for pancreatic cancer.
JOP
PUBLISHED: 07-31-2014
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Pancreatic cancer represents one of the leading causes of cancer related deaths worldwide and constitutes a major public health problem. Despite the advances in diagnosis and treatment, the overall five-year survival remains low, thus leading the focus of medical research towards the identification and modification of potential risk factors. This year, in ASCO Annual Meeting two interesting studies were presented. Ghani et al. (abstract #e15183) sought to investigate the effect of smoking on chemotherapy response in patients with metastatic pancreatic cancer, while Walker et al. (abstract #4117) presented the results of their study regarding the effect of statin use in the prevention of pancreatic cancer. Both studies concluded to useful results that along with the existing literature may further stimulate medical research towards better recognition of risk factors and the application of this knowledge in the clinical practice.
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Pain and Anxiety versus Sense of Family Support in Lung Cancer Patients.
Pain Res Treat
PUBLISHED: 07-13-2014
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Lung cancer is a stressful condition for both patient and family. The anxiety and pain accompanying cancer and its treatment have a significant negative influence on the patient's quality of life. The aim of this study was to investigate the correlation between anxiety, pain, and perceived family support in a sample of lung cancer patients. The sample consisted of a total of 101 lung cancer outpatients receiving treatment at the oncology department of a general hospital. Anxiety, pain (severity and impact on everyday life), and perceived family support were assessed using Spielberger's State-Trait Anxiety Inventory, the Brief Pain Inventory, and the Family Support Scale, respectively. Statistical analyses revealed correlations between anxiety, pain, and family support as perceived by the patients. The intensity of pain had a positive correlation with both state and trait anxiety and a negative correlation with family support. Anxiety (state and trait) had a significant negative correlation with family support. In conclusion, high prevalence rates of anxiety disorders were observed in lung cancer patients. Females appeared more susceptible to anxiety symptoms with a less sense of family support. A negative correlation was evidenced between family support and anxiety and a positive one between anxiety and pain.
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mTOR pathway: A current, up-to-date mini-review (Review).
Oncol Lett
PUBLISHED: 06-02-2014
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Mammalian target of rapamycin (mTOR) is a protein serine/threonine kinase that was initially identified as the cellular target of rapamycin. This kinase regulates cell growth, proliferation, motility and survival, as well as the gene transcription and protein synthesis that are activated in response to hormones, growth factors and nutrients. Results from preclinical studies have indicated that factors antagonizing the mTOR pathway exert an antitumor effect on lung cancer. Furthermore, primary clinical trials of mTOR inhibitors have demonstrated that the inhibitors may be effective against lung carcinoma. The present study explores the association between mTOR and lung carcinogenesis and describes the clinical trials of mTOR inhibitors.
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Pulmonary hypertension after pneumonectomy for lung cancer.
Asian Cardiovasc Thorac Ann
PUBLISHED: 03-17-2014
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We aimed to consolidate our clinical observations regarding the development of pulmonary hypertension following pneumonectomy for lung cancer.
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Metachronous and Synchronous Primary Lung Cancers: Diagnostic Aspects, Surgical Treatment, and Prognosis.
Clin Lung Cancer
PUBLISHED: 03-02-2014
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The average lifelong rate of developing a new primary lung cancer approximates 1% and 6% per year after radical therapy for non-small-cell lung cancer and small cell lung cancer, respectively. The frequency of recorded synchronous and metachronous lung cancers has been increasing in the recent years because of the development of early detection techniques and advances in cancer therapy. The distinction between multiple synchronous or metachronous primary lung cancers and intrapulmonary metastases is based on established clinicopathological criteria, however it is often difficult, although of great importance for the management and prognosis of these patients. Newly developed molecular and genomic methods are expected to contribute to a more solid and clear differentiation. Surgical treatment, whenever feasible, is considered the modality of choice for the management of patients with second primary lung cancers, as opposed to those with metastases. The type and extent of surgery are under discussion. The prognosis of patients with second primary lung cancers largely depends on the time of detection and the stage and location of the second cancer, thus surveillance after surgical resection of the initial tumor is mandatory.
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Biomarkers in pancreatic neuroendocrine tumors.
JOP
PUBLISHED: 02-06-2014
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The aim of biomarkers is to identify patients most likely to benefit from a therapeutic strategy. Pancreatic neuroendocrine tumors are rare neoplasms that arise in the endocrine tissues of the pancreas. Pancreatic neuroendocrine tumors represent 3% of primary pancreatic neoplasms and their incidence has risen. The SMAD4 gene is located on chromosome 18q and someday the SMAD4 gene status may be useful for prognostic stratification and therapeutic decision. The cells respond to environmental signals by modulating the expressions of genes contained within the nucleus, when genes are activated are transcribed to generate messenger RNA (mRNA). The examination of multiple expressed genes and proteins provides more useful information for prognostication of individual tumors. Here we summarize and discuss findings presented at the 2014 ASCO Gastrointestinal Cancers Symposium. Anna Karpathakis et al. (Abstract #212) reported data about the role of DNA methylation in gastrointestinal neuroendocrine tumors. Christina Lynn Roland et al. (Abstract #250) looked the impact Of SMAD4 on oncologic outcomes. Bong Kynn Kang et al. (Abstract #251) investigated prognostic biomarker using microRNA array technology.
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The role of biliary drainage in patients with pancreatic adenocarcinoma.
JOP
PUBLISHED: 02-05-2014
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Pancreatic cancer is one of the leading causes of cancer deaths worldwide and constitutes a major public health problem. One of the most common symptoms associated with pancreatic adenocarcinoma is jaundice, caused by the obstruction of common bile duct. Endobiliary stenting is used to relief these patients either preoperatively or merely for palliation and plastic or metal stents are usually endoscopically or percutaneously placed. Two interesting studies were presented at the 2014 ASCO Gastrointestinal Cancers Symposium. Strom et al. sought to investigate the effect of preoperative biliary drainage on recurrence and survival and they concluded that percutaneous biliary decompression was an independent predictor of worse overall survival and was associated with non-significant increase in hepatic recurrence (Abstract #314). Montero et al. presented the results of their study regarding the cost-effectiveness of metal stents in patients with inoperable pancreatic cancer and they concluded that placement of metal biliary stents is cost saving, improves overall survival and quality-adjusted survival compared with plastic stents (Abstract #260). Both studies concluded to useful results that along with the existing literature and formulated guidelines may help the provision of more effective, higher quality management of these patients.
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Updates in management of ampullary carcinomas.
JOP
PUBLISHED: 02-01-2014
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Ampullary carcinomas are rare malignancies representing less than 1% of all gastrointestinal cancers. Given the low incidence rate, there is scarcity of data regarding the survival benefit of the treatment options available. In the 2014 ASCO Gastrointestinal Cancers Symposium there were two abstracts that discussed the role of pancreaticoduodenectomy and adjuvant radiation therapy in ampullary carcinoma. The first study (Abstract #366) demonstrated a decline in morbidity and mortality over time for pancreaticoduodenectomy making it a reasonable option for successful treatment of ampullary carcinoma. The second study (Abstract #282) showed that adjuvant radiation therapy in patients with T2 tumors had improved median survival times compared to patients that did not receive radiation therapy.
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FOLFIRINOX: from the ACCORD study to 2014.
JOP
PUBLISHED: 01-30-2014
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In the field of treatment of pancreatic cancer, there has been significant progress lately. After the ACCORD/PRODIGE-4 study, 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) became the standard combination for first-line chemotherapy. This led also to its use in the neoadjuvant setting in borderline resectable tumors, or locally advanced unresectable disease, improving the resectability and survival. The major disadvantage of this therapy is increased toxicity, limiting its use to young patients with no comorbidities. This arises the need to make dose reductions in clinical practice, with a possible drawback in effectiveness. The authors summarize three Abstracts (#256, #275, #305) presented at the 2014 ASCO Gastrointestinal Cancers Symposium which were focused in the use of modified forms of FOLFIRINOX, their toxicity profile and effectiveness. Reduced toxicity was observed, without affecting the effectiveness of the combination.
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The clinical significance of cytology versus histology-based diagnosis in small cell lung cancer: a retrospective study.
Lung Cancer
PUBLISHED: 01-25-2014
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The aim of this study was to investigate the clinical significance of cytology versus histology-based diagnosis among patients diagnosed with small cell lung cancer (SCLC).
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Giant tuberculin reaction associated with the homeopathic drug tuberculinum: a case report.
Clin. Infect. Dis.
PUBLISHED: 01-14-2014
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Giant reactions to the tuberculin skin test are extremely rare and have been previously reported almost exclusively in patients with lepromatous leprosy. We herein report a giant tuberculin reaction associated with the homeopathic drug Tuberculinum in a patient with no evidence of active tuberculosis or leprosy.
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Appropriate utilization of restricted antibiotics in a general hospital of a perfecture area in Greece.
Curr Drug Saf
PUBLISHED: 01-06-2014
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Over-consumption of antibiotics has led to increased bacterial resistance and higher prevalence of hospital -acquired infections, resulting in rising treatment costs and prolonged length of hospital stay. The purpose of the study was to correlate the use of restricted antibiotics with recommended diagnosis and cost.
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Interleukin-7 and interleukin-15 for cancer.
J Cancer
PUBLISHED: 01-01-2014
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Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer.
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Inhaled tyrosine kinase inhibitors for pulmonary hypertension: a possible future treatment.
Drug Des Devel Ther
PUBLISHED: 01-01-2014
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Pulmonary hypertension is a disease with severe consequences for the human body. There are several diseases and situations that induce pulmonary hypertension and are usually underdiagnosed. Treatments include conventional medical therapies and oral, inhaled, intravenous, and subcutaneous options. Depending on its severity, heart or lung transplant may also be an option. A possible novel treatment could be tyrosine kinase inhibitors. We conducted experiments with three jet nebulizers and three ultrasound nebulizers with erlotinib, gefitinib, and imatinib. Different residual cup designs and residual cup loadings were used in order to identify the best combination to produce droplets of less than 5 ?m in mass median aerodynamic diameter. We found that gefitinib could not be transformed into a powder, so conversion to an aerosol form was not possible. Our experiments indicated that imatinib is superior to erlotinib with regard to small droplet size formation using both inhaled technologies (1.37 ?m <2.23 ?m and 1.92 ?m <3.11 ?m, jet and ultrasound, respectively) and, at jet devices (1.37 ?m <1.92 ?m). Cup designs C and G contribute best to small droplet creation uniquely supporting and equally well the activity of both drugs. The disadvantage of the large droplets formed for erlotinib was offset when combined with residual cup C (1.37 ?m instead of 2.23 ?m). At a 2 mL dose, the facemask and cone mouthpieces performed best and evenly; the facemask and low dose were the best choice (2.08 ?m and 2.12 ?m, respectively). Erlotinib and imatinib can be administered as an aerosols, and further in vivo experimentation is necessary to investigate the positive effects of these drugs in the treatment of pulmonary hypertension.
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MET gene copy number predicts worse overall survival in patients with non-small cell lung cancer (NSCLC); a systematic review and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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MET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC.
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Necrosis and apoptotic index as prognostic factors in non-small cell lung carcinoma: a review.
Springerplus
PUBLISHED: 01-01-2014
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Necrosis and apoptosis represent two pathogenetically distinct types of cell death. Necrosis is associated with pathologic conditions while apoptosis is a physiological process of programmed cell death, which is associated with normal tissue growth and is frequently impaired in various forms of cancer. Tumor necrosis and apoptotic index (AI) have been previously evaluated as prognostic biomarkers in lung cancer, but their exact clinical value remains unclear. The aim of this study was to perform a systematic review of the MEDLINE literature on the prognostic significance of these histopathological markers in patients with non-small cell lung carcinoma (NSCLC). Although a substantial body of evidence suggests that tumor necrosis may be a strong predictor of aggressive tumor behavior and reduced survival in patients with NSCLC, the independent prognostic value of this biomarker remains to be firmly established. Furthermore, previous data on the prognostic significance of apoptotic index in NSCLC are relatively limited and largely controversial. More prospective studies are necessary in order to further validate tumor necrosis and AI as prognostic markers in NSCLC.
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Usefulness of endobronchial ultrasound (EBUS) in the diagnosis of peripheral pulmonary lesions in a general hospital.
In Vivo
PUBLISHED: 08-31-2013
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To investigate the efficiency of guided bronchoscopy compared to blind techniques in the study of non-visible pulmonary lesions.
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Programmed death ligand-1 expression in non-small cell lung cancer.
Lab. Invest.
PUBLISHED: 08-29-2013
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Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations. A control tissue microarray (TMA) was constructed using PD-L1-transfected cells, normal human placenta and known PD-L1-positive NSCLC cases. Only one of four antibodies against PD-L1 (5H1) validated for specificity on this TMA. In situ PD-L1 mRNA using the RNAscope method was similarly validated. Two cohorts of NSCLC cases in TMAs including 340 cases from hospitals in Greece and 204 cases from Yale University were assessed. Tumors showed PD-L1 protein expression in 36% (Greek) and 25% (Yale) of the cases. PD-L1 expression was significantly associated with tumor-infiltrating lymphocytes in both cohorts. Patients with PD-L1 (both protein and mRNA) expression above the detection threshold showed statistically significant better outcome in both series (log-rank P=0.036 and P=0.027). Multivariate analysis showed that PD-L1 expression was significantly associated with better outcome independent of histology. Measurement of PD-L1 requires specific conditions and some commercial antibodies show lack of specificity. Expression of PD-L1 protein or mRNA is associated with better outcome. Further studies are required to determine the value of this marker in prognosis and prediction of response to treatments targeting this pathway.
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Pleural lavage cytology: Where do we stand?
Lung Cancer
PUBLISHED: 07-21-2013
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Although a malignant pleural effusion is considered a manifestation of an advanced stage disease not amenable to curative resection in patients with non-small cell lung cancer, the same is not true in the case of the presence of malignant cells in the pleural cavity without an accompanying effusion, discovered incidentally during the operation with pleural lavage cytology (PLC). PLC is a diagnostic technique used to detect tumor cells and translate this finding to a prognostic index. Various reports have attempted to utilize the results of PLC and draw inferences regarding the origins of malignant cells in the pleural cavity, the association of these results with various disease characteristics and, most importantly, their impact on disease recurrence and survival. However, due to non-consistent techniques and protocols used to acquire the samples for cytological evaluation and assess their significance, results are inhomogeneous. Nevertheless, the entrance of malignant cells in the pleural cavity follows the rules posed by the natural disease process when discovered before pulmonary resection takes place, while surgical manipulations certainly play an important role in the case malignant cells are checked over after pulmonary resection. In addition, although the prognostic significance of a positive PLC result is indisputable and significantly decreases long-term survival in the majority of studies, this factor has not yet been incorporated into the TNM staging system. Lastly, some authors have advocated the use of some form of adjuvant treatment for those patients found with positive PLC results, based on the assumption that a curative resection followed by multiple pleural washings will not remove the entirety of the population of malignant cells present in the pleural space.
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The VEGF pathway in lung cancer.
Cancer Chemother. Pharmacol.
PUBLISHED: 06-26-2013
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Lung cancer is a disease whose prognosis has remained poor in the last decades. Recent advances in the understanding of the molecular pathways behind this disease have revealed several mediators of important tumor functions. One of these functions is angiogenesis, which is considered essential for tumor growth and propagation, and a key mediator promoting this process is the vascular endothelial growth factor (VEGF). In lung cancer, VEGF plays a significant role in establishing a vascular supply within the tumor. Thus, a new class of drugs has emerged, targeting its pathway, which has offered substantial, albeit small, improvements in patient prognosis.
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Thymoma and radiation therapy: a systematic review of medical treatment.
Expert Rev Anticancer Ther
PUBLISHED: 06-19-2013
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Thymoma is the most common tumor in the anterior mediastinum (50% in adults). This review presents an update of thymoma treatment, commonly based on the Masaoka clinical staging system. The best treatment option is complete resection with no adjuvant approach in early stages and complete response. For incomplete resection, postoperative radiotherapy is recommended (5-year survival: 50-60%). For unresectable disease, concurrent chemoradiotherapy is performed. In conclusion, high technology (3D radiotherapy, 4D radiotherapy, intensity-modulated radiotherapy, image-guided radiotherapy and computed tomography fusion with PET scan) optimizes tumor target definition and provides dose escalation.
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Preclinical research in treatment of pancreatic cancer.
JOP
PUBLISHED: 06-11-2013
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Pancreatic adenocarcinoma is an aggressive type of malignancy and remains a treatment-refractory cancer. Because of the few treatment options, understanding of the molecular mechanisms is necessary, for new drugs be developed against molecular targets. Two of the novel, promising regimens against molecular targets, NVP-BEZ235 and MSK-777, were examined in three preclinical studies performed in human pancreatic cell lines and mouse models and presented in the 2013 ASCO Annual Meeting. Two of the studies evaluated the role of NVP-BEZ235, an oral phosphatidylinositol-3-kinase (PI3K) inhibitor, in pancreatic cancer treatment, alone and in combination with nab-paclitaxel (Abstract #e15007) or gemcitabine (Abstract #e15070). The third study presents the effectiveness of the novel cell division cycle 7 (Cdc7) kinase inhibitor, MSK-777 (Abstract #e15059). All studies demonstrated promising results and further investigation is ongoing.
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Prognostic factors in pancreatic cancer.
JOP
PUBLISHED: 06-11-2013
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Pancreatic cancer is a frequent and lethal disease ranking fourth as a cause of cancer-related death in Western countries. There are patients, though, who respond well to chemotherapy and have a prolonged survival. There is an effort towards identification of specific characteristics of these tumor cells in order to identify those patients who will benefit from chemotherapy and use them as prognostic or predictive factors. This review is an update on the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting regarding the most important developments in this field for pancreatic cancer, as they were reported in Abstracts #4006, #4016, #4046, and #4060 and a discussion is presented about their application in clinical praxis.
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Endoscopic and endobronchial ultrasound-guided needle aspiration in the mediastinal staging of non-small cell lung cancer.
Anticancer Res.
PUBLISHED: 06-11-2013
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Invasive staging of mediastinal lymph nodes is recommended for the majority of patients with potentially resectable non-small cell lung cancer. In the past, blind transbronchial needle aspiration during bronchoscopy and mediastinoscopy, a surgical procedure conducted under general anesthesia, were the only diagnostic methods. The latter is still considered the gold standard; however, two novel, minimally-invasive techniques have emerged for the evaluation of the mediastinum: endoscopic (transesophageal) and endobronchial ultrasound--both performed using a dedicated echoendoscope, facilitating the ultrasound-guided, real-time aspiration of mediastinal lymph nodes. These methods are well-tolerated under local anesthesia and moderate sedation, with very low complication rates. Current guidelines on the invasive mediastinal staging of lung cancer still state that a negative needle aspiration result from these methods should be confirmed by mediastinoscopy. As more experience is gathered and echoendoscopes evolve, a thorough endosonographic evaluation of the mediastinum by both techniques, will obviate the need for surgical staging in the vast majority of patients and reduce the number of futile thoracotomies.
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Soluble ICAM-1 levels in small-cell lung cancer: prognostic value for survival and predictive significance for response during chemotherapy.
Med. Oncol.
PUBLISHED: 05-18-2013
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Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule, member of the immunoglobulin gene superfamily that seems to participate in the evolution of the metastatic process. We investigated the significance of baseline soluble ICAM-1 levels on the outcome of patients with small-cell lung cancer and whether soluble ICAM-1 is a predictive marker for objective response during and after chemotherapy in patients with small-cell lung cancer. Fifty patients with recently diagnosed small-cell lung cancer, as well as 27 healthy smokers, were enrolled. Blood samples were collected at the time of diagnosis, during and at the end of chemotherapy. Data were correlated with the characteristics of the patients and survival as well as with ICAM-1 predictive role for objective response. Statistical significant values of baseline soluble ICAM between patients and controls (p < 0.001) were observed. Multivariate analysis revealed an elevated risk of death of 9 % in the first year after diagnosis for every 10 units of increased soluble ICAM-1 at the baseline (p = 0.046). Performance status and disease stage were also independent prognostic factors. Patients with extensive disease who achieved an objective response during chemotherapy showed a significant decrease (25.8 %) in their soluble ICAM-1 levels compared with baseline levels (p = 0.001). Alongside performance status and disease stage, baseline soluble ICAM-1 could be evaluated as an additional prognostic factor in patients with small-cell lung cancer. Also, a possible role for soluble ICAM-1 may exist as a predictive marker for objective response during chemotherapy for patients with extensive disease (p = 0.001).
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Multimodal treatment strategies for elderly patients with head and neck cancer.
Cancer Treat. Rev.
PUBLISHED: 05-12-2013
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The population in developed countries is growing older and the number of elderly people annually diagnosed with head and neck cancers is expected to rapidly increase within the following decades, since these types of tumors are age-dependent. The vast majority of older head and neck cancer patients present with locally advanced disease and multimodality treatment, including surgery, radiation and/or chemotherapy, is considered the best therapeutic option for these patients. However, several factors, including comorbidities, disabilities, frailty, and impaired functional status are considered to be more relevant criteria than chronological age per se for treatment planning. Therapeutic decisions are often complicated and demand the participation of many specialists. Advances in surgical and radiation techniques, along with the use of conventional chemotherapy and molecularly targeted agents, have improved treatment outcomes. The best-tailored individualized therapeutic option should be selected for these patients in order to avoid high toxicity and major functional deterioration. Still, more older-specific studies are needed in order to produce more definitive and applicable results. The aim of this review article is to investigate the multimodal treatment approaches for elderly patients with head and neck cancer.
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Time recall; future concept of chronomodulating chemotherapy for cancer.
Curr Pharm Biotechnol
PUBLISHED: 05-07-2013
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The human metabolism is regulated by our internal clock; the circadian rhythm (24h-25h). There are several factors included in the regulatory pathway such as; genes (PER1-3), (CRY1-2), TIM hormones (cortisol, catecholamines, melatonin and insulin) drugs, enzymes, sleep disorders and diseases. Each one contributes in a different degree and in order to enhance the therapeutic result; we should include these factors into clusters instead of targeting each factor one by one. Malignances deregulate gene-protein expression/production, enzyme production, and in addition they induce fatigue, insomnia, stress and sleep disorders. All these factors finally contribute in minimizing the efficiency of chemotherapy treatment and quality of life. In addition, the circadian rhythm disruption induces tumor genesis, stress, and downregulates the defense and repair mechanisms of the human body. In the current mini review the underlying mechanism of the circadian rhythm is provided, along with the influence of sleep disturbances in cancer patient therapy. A proposal is presented to divide circadian rhythm and sleep disturbances into two major clusters with different management, however; with a common target to improve treatment efficiency and quality of life. Finally, a chrono-chemotherapy administration model is proposed in order to have less chemotherapy side effects.
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Histones and lung cancer: Are the histone deacetylases a promising therapeutic target?
Cancer Chemother. Pharmacol.
PUBLISHED: 04-07-2013
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Deoxyribonucleic acid is wrapped around an octamer of core histone proteins to form a nucleosome, the basic structure of chromatin. Two main families of enzymes maintain the equilibrium of acetyl groups added to or removed from lysine residues. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues in histone amino termini and non-histone proteins also, leading to chromatin condensation and transcriptional repression. HDAC overexpression, resulting in tumor suppressor genes silencing, has been found in several human cancer tissues, indicating that aberrant epigenetic activity is associated with cancer development. Therefore, inhibitors of these enzymes are emerging anticancer agents and there is evidence supporting their role in hematological malignancies. The minimal efficacy of conventional chemotherapy has prompted a renewed focus on targeted therapy based on pathways altered during the pathogenesis of lung cancer. We identify the pleiotropic antitumor effects of HDAC inhibitors in lung cancer, focusing on the result caused by their use individually, as well as in combination with other chemotherapeutic agents, in lung cancer cell lines and in clinical trials.
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Lung cancer in never smokers: Disease characteristics and risk factors.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 03-24-2013
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It is estimated that approximately 25% of all lung cancer cases are observed in never-smokers and its incidence is expected to increase due to smoking prevention programs. Risk factors for the development of lung cancer described include second-hand smoking, radon exposure, occupational exposure to carcinogens and to cooking oil fumes and indoor coal burning. Other factors reported are infections (HPV and Mycobacterium tuberculosis), hormonal and diatery factors and diabetes mellitus. Having an affected relative also increases the risk for lung cancer while recent studies have identified several single nucleotide polymorphisms associated with increased risk for lung cancer development in never smokers. Distinct clinical, pathology and molecular characteristics are observed in lung cancer in never smokers; more frequently is observed in females and adenocarcinoma is the predominant histology while it has a different pattern of molecular alterations. The purpose of this review is to summarize our current knowledge of this disease.
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Multiplex PCR-based detection of circulating tumor cells in lung cancer patients using CK19, PTHrP, and LUNX specific primers.
Clin Lung Cancer
PUBLISHED: 02-19-2013
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The aim of this study was to develop a multiplex polymerase chain reaction (PCR)-based method for detection of circulating tumor cells in peripheral blood of lung cancer (LC) patients.
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The prognostic role of ephrin A2 and endothelial growth factor receptor pathway mediators in patients with advanced colorectal cancer treated with cetuximab.
Clin Colorectal Cancer
PUBLISHED: 02-13-2013
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Patients with colorectal cancer (CRC) with wild-type KRAS mutations are often treated with the endothelial growth factor receptor (EGFR) monoclonal antibody cetuximab. Despite the presence of a specific molecular target, most patients still do not derive benefit from this biological treatment. Our study explores the role of ephrin A2 (EphA2) receptor expression and of EGFR pathway mediators as predictors of cetuximab benefit.
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Novel agents in the treatment of pancreatic adenocarcinoma.
JOP
PUBLISHED: 02-13-2013
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The development of new agents and treatment strategies against pancreatic adenocarcinoma is vital, given the poor prognosis of the patients with this particular type of cancer. Three novel compounds were tested at different phases of clinical research and the results were presented in the recent ASCO Gastrointestinal Cancers Symposium. FG-3019 inhibits the connective tissue growth factor which is important in the biology of pancreatic cancer and was shown to be relatively safe in a phase I study (Abstract #213). In addition, ASG-5ME, an antibody specific for SLC44A4 that is universally expressed in pancreatic cancer and also carries a conjugate chemotherapy particle was safe at the appropriate dosing in a phase I trial (Abstract #176). Last but not least, tanespimycin, a molecule that inhibits heat shock protein 90 was not effective in the first line treatment of patients with pancreatic cancer in a phase II study (Abstract #245). Further studying of FG-3019 and ASG-5ME will show the potential activity if any of these compounds in patients with pancreatic cancer.
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Ampullary and periampullary adenocarcinoma: new challenges in management of recurrence.
JOP
PUBLISHED: 02-12-2013
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The mainstay treatment of ampullary and periampullary adenocarcinoma is pancreaticoduodenectomy. Unfortunately, there are no standard options available in the postoperative management due to the rarity of the malignancy and the absence of prospective trials. In this year ASCO Gastrointestinal Cancers Symposium three remarkable abstracts regarding the management of recurrent or metastatic ampullary and periampullary carcinoma were presented. The first study (Abstract #257) demonstrates that palliative reoperation should not be an option, because of its severe morbidity and high mortality. The second study (Abstract #317) supports that reirradiation is well tolerated and it could be used for palliative reasons and local control. The last study (Abstract #197) reveals the prognostic value of 92-gene RT-PCR assay and the authors support the use of this method for the management of metastatic periampullary adenocarcinoma when the primary pathological sample cannot be helpful.
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Pancreatic cancer: updates on translational research and future applications.
JOP
PUBLISHED: 02-12-2013
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Pancreatic cancer is one of the most lethal malignancies with a mortality rate almost equal to its incidence. It is ranked as the fourth leading cause of cancer-related deaths in the United States, and despite intensive basic and clinical research over the last few years, the survival benefit for the majority of patients with pancreatic cancer is still disappointing. Due to the absence of specific symptoms and the lack of early detection tests, pancreatic cancer is usually diagnosed at an advanced inoperrable stage and palliative chemotherapy with the purine analogue gemcitabine in combination with the targeted agent erlotinib, remains the mainstay method in the management of these patients. Therefore, there is an imperative need for new findings in the translational research field with prognostic, predictive and therapeutic value. In this paper we summarize five most interesting research abstracts as presented at the 2013 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #141 which investigates the interaction between liver and pancreatic organ damage in patients with pancreatic cancer and the potential contribution of the patatin-like phospholipase domain containing 3 (PNPLA3) gene variation in pancreatic cancer development and on Abstract #149, in which, the prognostic and predictive role of SWI/SNF complex, a chromatin-remodeling complex, is examined. The key role of pharmacogenomics, in terms of predicting response and resistance to chemotherapy in pancreatic cancer patients, is analyzed in Abstract #142 and the contribution of circulating tumor cell detection in the early diagnosis of pancreatic cancer, allowing the avoidance of more invasive procedures like EUS-FNA, is discussed in Abstract #157. Lastly, in Abstract #164, the diagnostic utility of YKL-40 and IL-6 in pancreatic cancer patients is investigated.
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Intraductal papillary mucinous neoplasms of the pancreas (IPMNs): epidemiology, diagnosis and future aspects.
JOP
PUBLISHED: 02-12-2013
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Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are potentially malignant intraductal epithelial neoplasms which consist of columnar, mucin-containing cells and arise from the epithelium of the main pancreatic duct or its branches. IPMNs as well as pancreatic intraepithelial neoplasias (PanINs) and mucinous cystic neoplasms represent noninvasive precursors of invasive ductal adenocarcinoma of the pancreas. The diagnosis of IPMNs includes radiographic (CT scanning, MRI, MRCP) and endoscopic evaluation (ERCP, EUS), PET, as well as serum tumor markers and molecular markers. The Sendai Consensus Guidelines help guide surgical resection for patients with IPMN. The follow-up of these patients, as well as of those who do not undergo surgical resection, is of great importance, since patients with IPMN appear to be at risk for other malignancies. Herein, the authors summarize the data presented at the 2013 ASCO Gastrointestinal Cancers Symposium regarding incidence and clinicopathological characteristics of IPMN (Abstracts #324, #187 and #179).
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Locally advanced pancreatic cancer.
JOP
PUBLISHED: 02-12-2013
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Treatment of locally advanced pancreatic cancer is palliative, based on chemotherapy and according to response, chemoradiotherapy can be applied. The authors summarize three abstracts (#LBA146, #256 and #303) presented on the 2013 ASCO Gastrointestinal Cancers Symposium, which were focused on treatment of locally advanced pancreatic cancer. A discussion is presented about the different chemotherapy or chemoradiotherapy regimens, that move away from gemcitabine-based treatment, and the effort to find less toxic, but efficient therapeutic combinations.
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Second-line therapy in pancreatic cancer.
JOP
PUBLISHED: 02-11-2013
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At the time of diagnosis most of patients present with advanced or metastatic pancreatic cancer, thereby precluding surgical resection. While the standard of care in the first line setting is established, there are limited data to support a standard second-line chemotherapy regimen. The authors summarize two interesting studies (Abstract #263 and Abstract #287) presented at the 2013 ASCO Gastrointestinal Cancers Symposium. These studies concern two phase II trials about second-line chemotherapy in pancreatic cancer. The first one evaluated the role of fluoropyrimidine as monotherapy versus fluoropyrimidine in combination with irinotecan (Abstract #263) and the second one compared the fluoropyrimidine treatment with the continuation of gemcitabine as monotherapy (Abstract #287).
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Clinical importance of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography in the management of patients with bronchoalveolar carcinoma: Role in the detection of recurrence.
Oncol Lett
PUBLISHED: 02-05-2013
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[(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been reported to have a low sensitivity in the initial diagnosis of bronchoalveolar carcinoma (BAC) due to BACs low metabolic activity. The aim of this study was to assess the value of [(18)F]FDG-PET/CT in the detection of BAC recurrence. Between February 2007 and September 2011, the [(18)F]FDG-PET/CT scans that were performed on patients with known, histologically proven BAC were studied. A total of 24 [(18)F]FDG-PET/CT scans were performed in 22 patients, including 16 males and 6 females, with a mean age of 65±9 years. Among the scans, 15 were performed to assess for possible recurrence with equivocal findings in conventional imaging methods and 9 for restaging post-therapy. In all cases conventional imaging studies (CT and MRI) were performed 5-30 days prior to PET/CT. Among the 24 [(18)F]FDG-PET/CT scans, 18 were positive and 6 negative. Among the 15 [(18)F]FDG-PET/CT scans performed for suspected recurrence, 34 lesions were detected and the mean maximum standardized uptake value (SUVmax) was 6.8±3.26. In nine scans, upstaging was observed, while two were in agreement with the findings of the conventional modalities. A greater number of lesions were detected in two scans and fewer lesions were detected in one, with no change in staging. Only one scan was negative. By contrast, in patients examined for restaging, there were only five lesions with a mean SUVmax of 4.86±3.18. Agreement between the findings of [(18)F]FDG-PET/CT and the conventional modalities was observed in 8 out of 9 cases. Although [(18)F]FDG-PET/CT has been reported to have a low sensitivity in the initial diagnosis of BAC, the present results indicate that when there is recurrence, the lesions become [(18)F]FDG avid. [(18)F]FDG-PET/CT may provide further information in patients evaluated for recurrence and thus improve patient management.
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Osteoporosis in patients with breast and prostate cancer: effect of disease and treatment modalities.
Endocr Metab Immune Disord Drug Targets
PUBLISHED: 01-18-2013
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The skeleton is constantly being remodelled through the simultaneous resorption of bone and formation of new bone. Significant effects on bone metabolism are produced due to cancer treatment especially of breast and prostate origin, even in the absence of bone metastases. These pathological changes are known as cancer treatment-induced bone loss. Bone mass loss and osteoporosis may cause an increased risk of fractures due to a reduction in bone volume and microarchitectural deterioration. On the other hand, the skeleton is both the most common organ affected by metastatic cancer and the site that produces the greatest morbidity for patients. Recent advances in our understanding of bone biology and the pathways by which cancer metastasizes and spreads to bone have contributed to the development of several important new drugs targeting these processes. This article summarizes our current knowledge and recommendations to advanced biology of metastasis, focusing on breast and prostate cancer.
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Key molecular mechanisms in lung cancer invasion and metastasis: a comprehensive review.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 01-16-2013
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Lung cancer remains one of the most common and malignant cancers worldwide. It is most often diagnosed at late stages, when it has already presented local invasion and distal metastases. The basic stages of invasion and metastasis involve the detachment of tumor cells from the extracellular matrix, invasion of surrounding tissues and basal lamina, intravasation into the blood stream, survival and transport through the blood stream, migration, arrest and extravasation at a distal site and formation of a metastatic lesion. These steps require fundamental mechanisms such as angiogenesis, degradation of matrix barriers, disruption of cell-cell and cell-matrix adhesion and inducement of cellular motility. Genes that regulate functions like unlimited growth potential, survival, genomic instability, angiogenesis, epithelial to mesenchymal transition and apoptosis evasion, are involved in giving lung cancer tumors invasive and metastatic competence. Improving of understanding of the underlying molecular and cellular mechanisms remains an urgent and essential issue, in order to develop new more effective strategies in preventing and treating lung cancer.
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Measurement of exhaled alveolar nitrogen oxide in patients with lung cancer: a friend from the past still precious today.
Onco Targets Ther
PUBLISHED: 01-01-2013
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Nitric oxide (NO) is a marker of airway inflammation and indirectly a general indicator of inflammation and oxidative stress. NO is a contributing factor in lung cancer at an early stage and also after chemotherapy treatment of lung cancer. We studied whether exhaled NO levels were altered by three cycles of chemotherapy at diagnosis and after chemotherapy, and whether, directly or indirectly, these changes were related to the course of disease. Also, a correlation of NO levels with other markers of inflammation was performed. We studied 42 patients diagnosed early: 26 men and 16 women with lung cancer. We analyzed blood tests for control of inflammatory markers, functional pulmonary tests, and alveolar exhaled NO. We recorded a decrease in exhaled NO after three cycles of chemotherapy in all patients, regardless of histological type and stage: there were 42 patients with mean 9.8 NO after three cycles (average 7.7). Also, a strong correlation appeared between NO measurements before and after chemotherapy and C-reactive protein (P < 0.05, r = 0.42, before) and (P < 0.045, r = 0.64, after). NO alveolar measurement as an indicator of airway inflammation indicates response to chemotherapy in lung cancer. Also, the inflammatory process in lung cancer was confirmed and indicated response to chemotherapy through an index that is sensitive to inflammatory disease of the airways.
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Role of positron emission tomography in the early prediction of response to chemotherapy in patients with non--small-cell lung cancer.
Clin Lung Cancer
PUBLISHED: 04-03-2011
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In recent years, molecular imaging with [(18)F]fluorodeoxyglucose-positron-emission tomography, [(18)F]FDG-PET, has become part of the standard of care in initial staging of patients with non-small-cell lung cancer. Currently, there is an increasing interest in the role of [(18)F]FDG-PET in the evaluation of biological characteristics of the tumor and the prediction of response to anticancer therapies at an early phase of treatment. According to the existing data, quantitative assessment of therapy-induced changes in tumor [(18)F]FDG uptake may allow the prediction of tumor response and patient outcome very early in the course of therapy. Treatment may be adjusted according to the chemosensitivity of the tumor tissue in an individual patient. Thus, [(18)F]FDG-PET has the potential to reduce the side effects and costs of ineffective therapy. This review provides an update on recent studies that evaluate the role of [(18)F]FDG-PET in the early prediction of response to chemotherapy and prognosis in patients with non-small-cell lung cancer. In addition, it discusses the application of [(18)F]FDG-PET to the monitoring of new targeted forms of anticancer therapy and particularly of epidermal growth factor receptor tyrosine kinase inhibitors. Finally, it evaluates the usefulness of [(18)F]fluorothymidine, a PET tracer for imaging tumor proliferation, in predicting response to therapy in patients with lung cancer.
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Standardization of epidermal growth factor receptor (EGFR) measurement by quantitative immunofluorescence and impact on antibody-based mutation detection in non-small cell lung cancer.
Am. J. Pathol.
PUBLISHED: 03-24-2011
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Challenges in measurement of epidermal growth factor receptor (EGFR) protein expression have led to conflicting data on its prognostic value and discontinuation of its use for prediction of response. Herein is described a quantitative standardized assay for EGFR and its use in a series of retrospective cohorts of patients with non-small cell lung cancer (NSCLC). The AQUA technology of quantitative immunofluorescence was used in conjunction with Western blot analysis to calculate the absolute concentration of EGFR in two independent NSCLC cohorts (170 from Yale New Haven Hospital and 335 from Sotiria and Patras Hospitals in Greece). EGFR and mutated EGFR were measured using D38B1 antibody and two mutation-specific antibodies. All patients positive or borderline for mutation-specific antibody were genotyped. A threshold for reproducible detection of EGFR was defined as 0.85 ng/?g total protein. EGFR expression demonstrated no prognostic value in either cohort. The mutation rate was 1.79% in the Yale cohort, and 1.52% in the Sotiria/Patras cohort, with no antibody detection-based false-positive cases. No mutations were detected for EGFR concentrations <1.46 ng/?g total protein. In summary, accurate measurement of EGFR still shows no prognostic value in NSCLC. In these two population-based cohorts, the antibody-based EGFR mutation rate was lower than has been frequently reported.
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Translational research in pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.
JOP
PUBLISHED: 03-10-2011
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The high mortality rate of pancreatic cancer places this uncommon malignancy quite high as a cause of cancer related deaths. Compared to other solid tumors, there is a lag in the development of new effective drugs and the actual clinical benefit remains poor over the last decade or so. The lack of therapeutic options necessitates the invention of the important molecules playing role in pancreatic carcinogenesis and the development of specific targeted therapies. Treatment advances have to be proven first in the bench before applying them at the bedside, thus why translational research is so needed. At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, preclinical evidence was presented regarding the efficacy of C4 compound against focal adhesion kinase (FAK) (Abstract #214), the role of the cyclooxygenase-2 (COX-2) inhibitor apricoxib in enhancing the efficacy of gemcitabine and erlotinib (Abstract #227) and the role of curcumin and ABT-888 (a poly-ADP ribose polymerase (PARP) inhibitor) as potent radiosensitizers (Abstracts #222 and #203). Interestingly, the invention of a novel monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic and colon cancer cell lines exhibited notable antibody-dependent cellular cytotoxicity (Abstract #235). Finally, enhanced selective targeting of pancreatic tumors was achieved by combining antibody-drug conjugates (ADC) with radioimmunotherapy (Abstract #206).
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Pancreatic neuroendocrine tumors: role of novel agents. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.
JOP
PUBLISHED: 03-10-2011
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Neuroendocrine tumors of pancreas (PNET) are very rare, consisting of heterogeneous histological subtypes with a variable natural history and different clinical manifestations. Although the vast majority of these neoplasms are sporadic, it is possible to be part of a genetic syndrome such as multiple endocrine neoplasia 1 (MEN-1) or tuberous sclerosis (TSC). When systemic treatment is required the options are limited and management strategy is generally based on experts consensus or clinical experience. The prognosis is usually better than in pancreatic adenocarcinoma, though poorly differentiated PNET behave aggressively and survival is shortened. Since last year, there has been a significant advance in the management of PNET, after reported data confirmed the efficacy of everolimus, an mTOR inhibitor, in patients with advanced disease. At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Symposium, updated results of the phase III trial (RADIANT-3) regarding the efficacy of everolimus in PNET (Abstract #158) were reported, along with the results of a subgroup analysis of the Japanese patients enrolled in this study (Abstract #289). Another agent with promising activity in PNET which will be discussed in this review is sunitinib, a biological agent with multikinase inhibitor properties (Abstract #244).
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Novel agents in the management of pancreatic adenocarcinoma: phase I studies. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.
JOP
PUBLISHED: 03-10-2011
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Pancreatic adenocarcinoma has repetitively proved refractory to chemotherapy and biologic compounds with only a few drugs offering limited benefit. A number of novel regimens has been tested in phase I trials and reported recently in the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. Specifically, a novel mitogen-activated protein kinase kinase (MEK) inhibitor, a connective tissue growth factor inhibitor, a coagulase factor VIIa inhibitor, as well as adenovirus delivery of herpes simplex virus thymidine synthase gene followed by anti-herpetic treatment have all proven to be safe in pancreatic cancer patients. Phase II trials will provide further evidence whether they can become clinically relevant in the future.
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Treatment for refractory pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.
JOP
PUBLISHED: 03-10-2011
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While gemcitabine-based regimens are currently accepted as the standard first-line treatment of patients with locally advanced or metastatic pancreatic adenocarcinoma, there is no consensus regarding treatment in the second-line setting. This review is an update from the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments in the treatment of refractory pancreatic cancer, as these were presented in Abstracts #237 and #272 of the meeting.
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Novel modalities in the treatment of patients with KRAS-mutated colorectal cancer.
Anticancer Drugs
PUBLISHED: 02-03-2011
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Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene are a well-described mechanism of resistance to monoclonal antibodies that target the epidermal growth factor receptor in patients with metastatic and nonoperable colorectal cancer. Treatment options in this population are limited to conventional chemotherapy regimens and antiangiogenesis compounds. Numerous strategies have been proposed in preclinical models as being effective in the presence of KRAS mutations. As basic and translational research further unravels the complex interactions and regulation points in the pathways downstream of epidermal growth factor receptor, more drugs become available for clinical testing. Indeed, there are many ongoing clinical trials that focus on the safety and efficacy of novel compounds in patients with KRAS-mutated colorectal cancer. This is a review of the literature with regard to the rationale of various approaches on this topic and also a summary of the current active clinical trials limited to patients with KRAS-mutated colorectal cancer.
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STAT-Related Profiles Are Associated with Patient Response to Targeted Treatments in Locally Advanced SCCHN.
Transl Oncol
PUBLISHED: 02-01-2011
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The anti-epidermal growth factor receptor antibody cetuximab (Erbitux, CTX) is currently used for the treatment of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), as yet with modest effectiveness, prompting for the identification of response predictors to this treatment and for the targeting of additional pathways implicated in this disease. Within this scope, we investigated the effect of SRC/STAT pathway components on LA-SCCHN patient outcome. SRC, STAT1, STAT3, STAT5A, STAT5B, ANXA1, CAV1, IGFBP2, EPHA2, EPHB2, and MSN relative gene expression, as well as Stat protein activation, were assessed on LA-SCCHN tumor tissues from 35 patients treated with combined radiotherapy (RT) and CTX-based regimens. Stat1, Stat3, and Stat5 proteins were usually found activated in neoplastic nuclei (70.4%, 85.7%, and 70.8%, respectively). Activated Stat3 and Stat5 were associated with each other (P = .017) and with a CAV1(high)/MSN(high)/IGFBP2(low) profile. All patients with tumors expressing high STAT5A/EPHA2 experienced a complete response on RT-CTX-based treatments (12/15 complete responders, P < .0001) and a longer progression-free survival (P = .024). Few tumors expressed high ANXA1/CAV1/EPHA2 and low IGFBP2, a putative dasatinib response-related profile, whereas high ANXA1 was associated with shorter overall survival (P = .003). In conclusion, Stat activation is common in LA-SCCHN, where overexpression of STAT5A and EPHA2 may predict for response to RT-CTX treatments. The STAT5A/EPHA2 profile seems of particular interest for validation in larger cohorts and in multiple tumor types because markers for the positive selection of patients to benefit from CTX-containing treatments are currently lacking.
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Molecular classification of nonsmall cell lung cancer using a 4-protein quantitative assay.
Cancer
PUBLISHED: 01-31-2011
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The importance of definitive histological subclassification has increased as drug trials have shown benefit associated with histology in nonsmall-cell lung cancer (NSCLC). The acuity of this problem is further exacerbated by the use of minimally invasive cytology samples. Here we describe the development and validation of a 4-protein classifier that differentiates primary lung adenocarcinomas (AC) from squamous cell carcinomas (SCC).
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Prospective comparison of peritumoral and subareolar injection of blue dye alone, for identification of sentinel lymph nodes in patients with early stage breast cancer.
J Surg Oncol
PUBLISHED: 01-28-2011
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Various techniques are used for the identification of the sentinel node (SLN). We prospectively compare the efficacy of SLN biopsy and the number of SLNs identified, by injecting methylene blue (MB) alone in the subareolar area (SA) or peritumorally (PT) in patients with early stage breast cancer.
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Breast angiosarcoma that is not related to radiation exposure: a comprehensive review of the literature.
Surg. Today
PUBLISHED: 01-26-2011
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Breast angiosarcomas that are not related to previous radiotherapy are very rare. Surgical resection is the primary treatment for these tumors, but there is no general agreement on the extent of surgery. The role of multimodality adjuvant treatment also remains controversial. The aim of this study was to summarize the available data from the largest published series of patients in terms of management and outcome. We also sought to identify prognostic factors influencing patient survival. We have included studies presenting detailed data on multimodality therapy and survival of patients with breast angiosarcoma. Ten studies presenting data on 280 patients were included in the review. Seventy-five percent of patients underwent a total mastectomy and 25% had breast-conserving treatment (BCT). In 42% of patients, an axillary node dissection was combined with mastectomy or BCT. Thirty-six percent of patients received chemotherapy and 35% were treated with radiotherapy in an adjuvant or neoadjuvant setting. Survival varied significantly according to tumor size and grade. Adjuvant multimodality therapy may improve the outcome in selected patients with breast angiosarcoma. Tumor size, grade, and margin status are the most important prognostic factors for survival.
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Recent advances in molecular diagnosis of thyroid cancer.
J Thyroid Res
PUBLISHED: 01-24-2011
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Recent molecular studies have described a number of abnormalities associated with the progression and dedifferentiation of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development. In particular, remarkable advances have occurred in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. Recognition of these features is crucial to the management of patients with thyroid cancer. Novel treatments are being designed based on our enhanced understanding of this disease process.
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Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients.
Virchows Arch.
PUBLISHED: 08-11-2010
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Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multiplexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p?=?0.03), VEGFD (p?
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Pharmacogenetics and other molecular targets in the management of pancreatic adenocarcinoma. Highlights from the "2010 ASCO Annual Meeting". Chicago, IL, USA. June 4-8, 2010.
JOP
PUBLISHED: 07-06-2010
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Among various abstracts presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) held in Chicago, June 2010, four interesting abstracts focusing on pancreatic cancer merit further discussion in this post-ASCO commentary as they potentially provide insight to clinicians and hope to patients. These abstracts point to the future of pancreatic cancer management through identification of molecular targets and prognostic factors to overcome the limits of efficacious chemotherapy delivery.
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Novel agents for the treatment of pancreatic adenocarcinoma: any light at the end of the tunnel? Highlights from the "2010 ASCO Annual Meeting". Chicago, IL, USA. June 4-8, 2010.
JOP
PUBLISHED: 07-06-2010
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Pancreatic cancer is a disease with dismal prognosis and treatment options are limited. Development of novel active compounds is mandatory. A number of pancreatic cancer clinical trials that included a novel agent among their arms were presented at the recent 2010 American Society of Clinical Oncology (ASCO) Annual Meeting. It appears that IGF-1R inhibition might be effective and this should be tested in further trials. Microtubule stabilization with ixabepilone in combination with EGFR does not lead to promising improvement in prognosis whereas nab-paclitaxel in combination with anti-angiogenetic agents is a combination not previously tested that showed an acceptable safety profile. This combination might be worth testing in a phase II clinical trial. Last but not least, CTLA-4 blockade has an acceptable toxicity profile but its efficacy needs to be proven over placebo in phase II and III trials. Finally, understanding of the tumor biology and biomarker analysis from the clinical trials is warranted.
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Therapeutic effect of sodium iodide symporter gene therapy combined with external beam radiotherapy and targeted drugs that inhibit DNA repair.
Mol. Ther.
PUBLISHED: 06-29-2010
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Adenoviral (AdV) transfer of sodium iodide symporter (NIS) gene has translational potential, but relatively low levels of transduction and subsequent radioisotope uptake limit the efficacy of the approach. In previous studies, we showed that combining NIS gene delivery with external beam radiotherapy (EBRT) and DNA damage repair inhibitors increased viral gene expression and radioiodide uptake. Here, we report the therapeutic efficacy of this strategy. An adenovirus expressing NIS from a telomerase promoter (Ad-hTR-NIS) was cytotoxic combined with relatively high-dose (50 microCi) (131)I therapy and enhanced the efficacy of EBRT combined with low-dose (10 and 25 microCi) (131)I therapy in colorectal and head and neck cancer cells. Combining this approach with ataxia-telangiectasia mutated (ATM) or DNA-dependent protein kinase (DNA-PK) inhibition caused maintenance of double-stranded DNA breaks (DSBs) at 24 hours and increased cytotoxicity on clonogenic assay. When the triplet of NIS-mediated (131)I therapy, EBRT, and DNA-PKi was used in vivo, 90% of mice were tumor-free at 5 weeks. Acute radiation toxicity in the EBRT field was not exacerbated. In contrast, DNA-PKi did not enhance the therapeutic efficacy of EBRT plus adenovirus-mediated HSVtk/ganciclovir (GCV). Therefore, combining NIS gene therapy and EBRT represents an ideal strategy to exploit the therapeutic benefits of novel radiosensitizers.
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High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology.
BMC Cancer
PUBLISHED: 05-09-2010
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Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results.
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Clinical pharmacogenetics in oncology: the paradigm of molecular targeted therapies.
Curr. Pharm. Des.
PUBLISHED: 04-19-2010
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Even though treatment of several types of solid tumors has improved in the past few years with the introduction of molecular targeted agents in the therapeutic armamentarium of the medical oncologist, response rates to these agents are generally modest. Increasing evidence is now revealing that genetic factors are affecting patients response to these therapeutic agents as well as the frequency and intensity of toxic reactions. Importantly, pharmacogenetic analysis is now required for the administration of several molecular targeted agents in clinical practice. For the vast majority of these agents, however, data remain purely experimental. Herein, we provide an overview of the genetic changes (mutations and polymorphisms) that have been associated with response to treatment with anticancer molecular targeted agents. Special emphasis is given on molecules (monoclonal antibodies and tyrosine kinase inhibitors) that target critical mediators in the epidermal growth factor receptor (EGFR), the human epidermal growth factor receptor 2 (HER2/ERBB2/NEU) and the vascular endothelial growth factor receptor (VEGFR) pathways. The true clinical utility of these applications remains to be proven in future prospective, randomized clinical trials in large patient cohorts of all different ethnic backgrounds.
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Quantitative evaluation of protein expression as a function of tissue microarray core diameter: is a large (1.5 mm) core better than a small (0.6 mm) core?
Arch. Pathol. Lab. Med.
PUBLISHED: 04-07-2010
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Tissue microarrays (TMAs) have emerged as a high-throughput technology for protein evaluation in large cohorts. This technique allows maximization of tissue resources by analysis of sections from 0.6-mm to 1.5-mm core "biopsies" of standard formalin-fixed, paraffin-embedded tissue blocks and by the processing of hundreds of cases arrayed on a single recipient block in an identical manner.
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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.