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pancreatic cancer molecular classification

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https://www.readbyqxmd.com/read/27647802/next-generation-sequencing-adds-value-to-the-preoperative-diagnosis-of-pancreatic-cysts
#1
Matthew W Rosenbaum, Martin Jones, Jonathan C Dudley, Long P Le, A John Iafrate, Martha B Pitman
BACKGROUND: The diagnosis of a pancreatic cyst as mucinous or high-risk dictates the need for follow-up or surgery. Molecular analysis of aspirated pancreatic cyst fluid (PCF) can provide valuable information not obtained by carcinoembryonic antigen (CEA) analysis or cytology. METHODS: All patients who underwent molecular analysis of PCF between March 2013 and June 2015 were reviewed, including pathology, imaging, and follow-up. Molecular testing was performed using a patented, anchored multiplex polymerase chain reaction next-generation sequencing (NGS) platform, which sequenced numerous hotspots in 39 genes linked with malignancy...
September 20, 2016: Cancer Cytopathology
https://www.readbyqxmd.com/read/27345450/-new-molecular-classification-of-colorectal-cancer-pancreatic-cancer-and-stomach-cancer-towards-%C3%A3-la-carte-treatment
#2
REVIEW
Chantal Dreyer, Pauline Afchain, Isabelle Trouilloud, Thierry André
This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion)...
July 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27225481/yin-yang-1-is-associated-with-cancer-stem-cell-transcription-factors-sox2-oct4-bmi1-and-clinical-implication
#3
REVIEW
Samantha Kaufhold, Hermes Garbán, Benjamin Bonavida
The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on these similarities, it was expected that YY1 expression would be associated with SOX2, OCT4, BMI1, and NANOG's expressions and activities...
2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/26883357/genetics-and-biology-of-pancreatic-ductal-adenocarcinoma
#4
REVIEW
Haoqiang Ying, Prasenjit Dey, Wantong Yao, Alec C Kimmelman, Giulio F Draetta, Anirban Maitra, Ronald A DePinho
With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses...
February 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/26857392/relevance-of-sp-binding-site-polymorphism-in-wwox-for-treatment-outcome-in-pancreatic-cancer
#5
Markus A Schirmer, Claudia M Lüske, Sebastian Roppel, Alexander Schaudinn, Christian Zimmer, Ruben Pflüger, Martin Haubrock, Jacobe Rapp, Cenap Güngör, Maximilian Bockhorn, Thilo Hackert, Thomas Hank, Oliver Strobel, Jens Werner, Jakob R Izbicki, Steven A Johnsen, Jochen Gaedcke, Jürgen Brockmöller, B Michael Ghadimi
BACKGROUND: A genome-wide association study (GWAS) suggested inherited genetic single-nucleotide polymorphisms (SNPs) affecting overall survival (OS) in advanced pancreatic cancer. To identify robust clinical biomarkers, we tested the strongest reported candidate loci in an independent patient cohort, assessed cellular drug sensitivity, and evaluated molecular effects. METHODS: This study comprised 381 patients with histologically verified pancreatic ductal adenocarcinoma treated with gemcitabine-based chemotherapy...
May 2016: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/26710214/astrocyte-elevated-gene-1-as-a-novel-clinicopathological-and-prognostic-biomarker-for-gastrointestinal-cancers-a-meta-analysis-with-2999-patients
#6
Yihuan Luo, Xin Zhang, Zhong Tan, Peirong Wu, Xuelian Xiang, Yiwu Dang, Gang Chen
BACKGROUND: There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients...
2015: PloS One
https://www.readbyqxmd.com/read/26417858/gene-signatures-from-pancreatic-cancer-tumor-and-stromal-cells-predict-disease-outcome
#7
COMMENT
Filippos Kottakis, Nabeel Bardeesy
Pancreatic cancers consist of a heterogeneous amalgam of assorted cell types, making it challenging to develop a classification system that groups these tumors according to common molecular features. A new study tackles this important issue using bioinformatics approaches to decipher gene expression signatures derived specifically from either tumor cells or nonmalignant stromal cells that predict patient outcome and may inform personalized treatments.
October 2015: Nature Genetics
https://www.readbyqxmd.com/read/25984514/epithelial-mesenchymal-mesenchymal-epithelial-and-endothelial-mesenchymal-transitions-in-malignant-tumors-an-update
#8
Simona Gurzu, Sabin Turdean, Attila Kovecsi, Anca Otilia Contac, Ioan Jung
Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET)...
May 16, 2015: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/25956813/-pulmonary-neuroendocrine-tumors-in-the-new-who-2015-classification-start-of-breaking-new-grounds
#9
P A Schnabel, K Junker
CLASSIFICATION: In the recently published 4th edition of the World Health Organization (WHO) classification of tumors of the lungs, pleura, thymus and heart, all neuroendocrine tumors of the lungs (pNET) are presented for the first time in one single chapter following adenocarcinoma and squamous cell carcinoma and before large cell carcinoma. In this classification, high grade small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are differentiated from intermediate grade atypical carcinoids (AC) and low grade typical carcinoids as well as from preinvasive lesions (DIPNECH)...
May 2015: Der Pathologe
https://www.readbyqxmd.com/read/25819575/histomorphologic-and-molecular-phenotypes-predict-gemcitabine-response-and-overall-survival-in-adenocarcinoma-of-the-ampulla-of-vater
#10
Tobias S Schiergens, Simone Reu, Jens Neumann, Bernhard W Renz, Hanno Niess, Stefan Boeck, Volker Heinemann, Christiane J Bruns, Karl-Walter Jauch, Axel Kleespies
BACKGROUND: The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). METHODS: Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study...
July 2015: Surgery
https://www.readbyqxmd.com/read/25807437/identification-of-mirna-mrna-crosstalk-in-pancreatic-cancer-by-integrating-transcriptome-analysis
#11
J Yang, Y Zeng
OBJECTIVE: Pancreatic cancer is one of the most lethal diseases, and the pathogenesis remains largely unknown. To this end, we performed an integrated analysis of miRNA and mRNA expression data to explore the deregulation of miRNA and mRNA and regulatory processes underlying pancreatic cancer. MATERIALS AND METHODS: We combined mRNA and miRNA expression data with miRNA target predictions to infer new miRNA regulation activities in pancreatic cancer. We first integrated miRNA and mRNA expression profiling separately to identify differently expressed miRNA and mRNA in pancreatic cancer...
2015: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/25733690/glycan-motif-profiling-reveals-plasma-sialyl-lewis-x-elevations-in-pancreatic-cancers-that-are-negative-for-sialyl-lewis-a
#12
Huiyuan Tang, Sudhir Singh, Katie Partyka, Doron Kletter, Peter Hsueh, Jessica Yadav, Elliot Ensink, Marshall Bern, Galen Hostetter, Douglas Hartman, Ying Huang, Randall E Brand, Brian B Haab
The sialyl-Lewis A (sLeA) glycan forms the basis of the CA19-9 assay and is the current best biomarker for pancreatic cancer, but because it is not elevated in ∼25% of pancreatic cancers, it is not useful for early diagnosis. We hypothesized that sLeA-low tumors secrete glycans that are related to sLeA but not detectable by CA19-9 antibodies. We used a method called motif profiling to predict that a structural isomer of sLeA called sialyl-Lewis X (sLeX) is elevated in the plasma of some sLeA-low cancers. We corroborated this prediction in a set of 48 plasma samples and in a blinded set of 200 samples...
May 2015: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/25726050/pathological-and-molecular-evaluation-of-pancreatic-neoplasms
#13
REVIEW
Arvind Rishi, Michael Goggins, Laura D Wood, Ralph H Hruban
Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives...
February 2015: Seminars in Oncology
https://www.readbyqxmd.com/read/25668599/increased-expression-of-the-lncrna-pvt1-is-associated-with-poor-prognosis-in-pancreatic-cancer-patients
#14
C Huang, W Yu, Q Wang, H Cui, Y Wang, L Zhang, F Han, T Huang
AIM: Long non-coding RNA PVT1 (lncRNA PVT1) has been identified and it plays an oncogenic role in various human cancers. However, its roles in pancreatic cancer remain unclear. The aim of this paper was to explore the PVT1 expression levels and relationship with survival of patients with pancreatic ductal adenocarcinoma (PDAC) and to establish the significance of PVT1 in the development and progression of PDAC. METHODS: In this study, quantitative real-time polymerase chain reaction was performed to analyze the expression levels of lncRNA PVT1 in paired PDAC and adjacent nontumor tissues...
June 2015: Minerva Medica
https://www.readbyqxmd.com/read/25605630/the-genetic-classification-of-pancreatic-neoplasia
#15
REVIEW
Hanno Matthaei, Alexander Semaan, Ralph H Hruban
Cancer is caused by the accumulation of inherited and/or acquired alterations in specific genes. The recent decline in the cost of DNA sequencing has allowed tumor sequencing to be conducted on a large scale, which, in turn, has led to an unprecedented understanding of the genetic events that drive neoplasia. This understanding, when integrated with meticulous histologic analyses and with clinical findings, has direct clinical implications. The recent sequencing of all of the major types of cystic and noncystic neoplasms of the pancreas has revealed opportunities for molecular diagnoses and for personalized treatment...
May 2015: Journal of Gastroenterology
https://www.readbyqxmd.com/read/25320520/pathology-of-pancreatic-ductal-adenocarcinoma-facts-challenges-and-future-developments
#16
REVIEW
Irene Esposito, Björn Konukiewitz, Anna Melissa Schlitter, Günter Klöppel
Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection...
October 14, 2014: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/25210494/metabolic-profiles-are-principally-different-between-cancers-of-the-liver-pancreas-and-breast
#17
Anuradha Budhu, Atsushi Terunuma, Geng Zhang, S Perwez Hussain, Stefan Ambs, Xin Wei Wang
Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens...
2014: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/24799949/utility-of-molecular-tests-in-cytopathology
#18
REVIEW
Arthur David Somoza, F Zahra Aly
With the popularity of interventional radiology, diagnostic material obtained can be limited requiring critical decisions on making the best use of it. Molecular testing using nanogram amounts of tissue can add useful diagnostic information by improving sensitivity and/or specificity of the diagnosis. This review examines the use of molecular tests in cervical cytology, "indeterminate" thyroid cytology specimens, pancreatic cyst fluid, urinary tract and pulmonary adenocarcinoma cytologic material. Molecular human papillomavirus (HPV) testing combined with cervical cytology increases sensitivity of detection of high grade lesions...
2014: CytoJournal
https://www.readbyqxmd.com/read/24604757/targeted-next-generation-sequencing-of-cancer-genes-dissects-the-molecular-profiles-of-intraductal-papillary-neoplasms-of-the-pancreas
#19
Eliana Amato, Marco Dal Molin, Andrea Mafficini, Jun Yu, Giuseppe Malleo, Borislav Rusev, Matteo Fassan, Davide Antonello, Yoshihiko Sadakari, Paola Castelli, Giuseppe Zamboni, Anirban Maitra, Roberto Salvia, Ralph H Hruban, Claudio Bassi, Paola Capelli, Rita T Lawlor, Michael Goggins, Aldo Scarpa
Intraductal neoplasms are important precursors to invasive pancreatic cancer and provide an opportunity to detect and treat pancreatic neoplasia before an invasive carcinoma develops. The diagnostic evaluation of these lesions is challenging, as diagnostic imaging and cytological sampling do not provide accurate information on lesion classification, the grade of dysplasia or the presence of invasion. Moreover, the molecular driver gene mutations of these precursor lesions have yet to be fully characterized...
July 2014: Journal of Pathology
https://www.readbyqxmd.com/read/24482424/imaging-mass-spectrometry-to-discriminate-breast-from-pancreatic-cancer-metastasis-in-formalin-fixed-paraffin-embedded-tissues
#20
Rita Casadonte, Mark Kriegsmann, Friederike Zweynert, Katrin Friedrich, Gustavo Baretton, Gustavo Bretton, Mike Otto, Sören-Oliver Deininger, Rainer Paape, Eckhard Belau, Detlev Suckau, Daniela Aust, Christian Pilarsky, Jörg Kriegsmann
Diagnosis of the origin of metastasis is mandatory for adequate therapy. In the past, classification of tumors was based on histology (morphological expression of a complex protein pattern), while supportive immunohistochemical investigation relied only on few "tumor specific" proteins. At present, histopathological diagnosis is based on clinical information, morphology, immunohistochemistry, and may include molecular methods. This process is complex, expensive, requires an experienced pathologist and may be time consuming...
April 2014: Proteomics
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