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intratumor heterogeneity

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https://www.readbyqxmd.com/read/29341153/circulating-tumour-cells-and-dna-as-liquid-biopsies-in-gastrointestinal-cancer
#1
REVIEW
O Nordgård, K Tjensvoll, B Gilje, K Søreide
BACKGROUND: Blood is the most extensively studied body fluid and, because it contains circulating tumour cells (CTCs) and circulating tumour-derived cell-free DNA (ctDNA), it may represent a liquid biopsy for cancer. Methods for enrichment and detection of CTCs and ctDNA, their clinical applications and future opportunities in gastrointestinal cancers were the focus of this review. METHODS: The PubMed database was searched for literature up to 24 June 2017, with a focus on the past 10 years...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29337243/intratumoral-morphological-heterogeneity-can-be-an-indicator-of-genetic-heterogeneity-in-colorectal-cancer
#2
Juliane Büttner, Korinna Jöhrens, Frederick Klauschen, Michael Hummel, Dido Lenze, Wolfgang Saeger, Annika Lehmann
Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with RAS wild-type. However, resistance to targeted therapy is often observed and can be primary or acquired. One reason for primary resistance is the presence of mutations that are undetected due to genetic heterogeneity, which can be expressed by differences present in primary tumor and distant metastasis or recurrence or by an intratumoral heterogeneity (presence of different subclones in the investigated tumor sample). The aim of our study was to investigate if morphological heterogeneity can be an indicator of intratumoral heterogeneity...
January 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#3
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29327728/diverse-modes-of-clonal-evolution-in-hbv-related-hepatocellular-carcinoma-revealed-by-single-cell-genome-sequencing
#4
Meng Duan, Junfeng Hao, Sijia Cui, Daniel L Worthley, Shu Zhang, Zhichao Wang, Jieyi Shi, Longzi Liu, Xiaoying Wang, Aiwu Ke, Ya Cao, Ruibin Xi, Xiaoming Zhang, Jian Zhou, Jia Fan, Chong Li, Qiang Gao
Hepatocellular carcinoma (HCC) is a cancer of substantial morphologic, genetic and phenotypic diversity. Yet we do not understand the relationship between intratumor heterogeneity and the associated morphologic/histological characteristics of the tumor. Using single-cell whole-genome sequencing to profile 96 tumor cells (30-36 each) and 15 normal liver cells (5 each), collected from three male patients with HBV-associated HCC, we confirmed that copy number variations occur early in hepatocarcinogenesis but thereafter remain relatively stable throughout tumor progression...
January 12, 2018: Cell Research
https://www.readbyqxmd.com/read/29325706/contrast-harmonic-eus-for-the-prediction-of-pancreatic-neuroendocrine-tumor-aggressiveness-with-videos
#5
Maxime Palazzo, Bertrand Napoléon, Rodica Gincul, Mathieu Pioche, Bertrand Pujol, Christine Lefort, Fabien Fumex, Vincent Hautefeuille, Monique Fabre, Jérome Cros, Michèle Felce, Anne Couvelard, Alain Sauvanet, Philippe Lévy, Philippe Ruszniewski, Laurent Palazzo
BACKGROUND AND AIM: Contrast-harmonic EUS (CH-EUS) has the ability to depict a tumor microvasculature. Decreased microvascular density has been identified as a factor associated with tumor aggressiveness. We aimed to study the accuracy of CH-EUS for the prediction of pancreatic neuroendocrine tumor (PNET) aggressiveness. METHODS: Between June 2009 and March 2015, all consecutive patients with histology-proven PNETs and CH-EUS examination were included. Nine endosonographers analyzed blindly all the videos...
January 8, 2018: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29315726/single-cell-analysis-reveals-cancer-stem-cell-heterogeneity-in-hepatocellular-carcinoma
#6
Hongping Zheng, Yotsawat Pomyen, Maria Olga Hernandez, Caiyi Li, Ferenc Livak, Wei Tang, Hien Dang, Tim F Greten, Jeremy L Davis, Yongmei Zhao, Monika Mehta, Yelena Levin, Jyoti Shetty, Bao Tran, Anuradha Budhu, Xin Wei Wang
Intratumor molecular heterogeneity of hepatocellular carcinoma (HCC) is partly attributed to the presence of hepatic cancer stem cells (CSCs). Different CSC populations defined by various cell surface markers may contain different oncogenic drivers, posing a challenge in defining molecular-targeted therapeutics. We combined transcriptomic and functional analyses of HCC cells at the single cell level to assess the degree of CSC heterogeneity. We provide evidence that hepatic CSCs at the single-cell level are phenotypically, functionally and transcriptionally heterogeneous...
January 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29312603/intratumoral-heterogeneity-and-tert-promoter-mutations-in-progressive-higher-grade-meningiomas
#7
Tareq A Juratli, Christian Thiede, Mara V A Koerner, Shilpa S Tummala, Dirk Daubner, Ganesh M Shankar, Erik A Williams, Maria Martinez-Lage, Silke Soucek, Katja Robel, Tristan Penson, Mechthild Krause, Steffen Appold, Matthias Meinhardt, Thomas Pinzer, Julie J Miller, Dietmar Krex, Heather A Ely, Ian M Silverman, Jason Christiansen, Gabriele Schackert, Hiroaki Wakimoto, Matthias Kirsch, Priscilla K Brastianos, Daniel P Cahill
Background: Recent studies have reported mutations in the telomerase reverse transcriptase promoter (TERTp) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods: We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311223/genomic-analyses-and-precision-oncology-in-gastroesophageal-cancer-forwards-or-backwards
#8
Raghav Sundar, Patrick Tan
Gastroesophageal adenocarcinoma (GEA) comprises a myriad of distinct subtypes with significant interpatient, intrapatient, and intratumor heterogeneity. Strategies for tackling molecular heterogeneity will be essential for the success of GEA precision oncology-in this regard, blood-based "liquid biopsies" may provide broader views of the real-time genomic landscape of this disease, identifying actionable biomarkers and monitoring therapy resistance. Cancer Discov; 8(1); 14-6. ©2018 AACRSee related article by Pectasides et al...
January 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29307488/multiclonal-invasion-in-breast-tumors-identified-by-topographic-single-cell-sequencing
#9
Anna K Casasent, Aislyn Schalck, Ruli Gao, Emi Sei, Annalyssa Long, William Pangburn, Tod Casasent, Funda Meric-Bernstam, Mary E Edgerton, Nicholas E Navin
Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29307361/role-of-the-blood-brain-barrier-in-metastatic-disease-of-the-central-nervous-system
#10
Anna S Berghoff, Matthias Preusser
Systemic therapy is an important backbone in the multimodal treatment approach of brain metastases. However, the blood-brain barrier or, more correctly, the blood-tumor barrier, as the properties of tumor-associated vessels differ from the physiologic state, potentially limits the passage of systemic drugs. Indeed, several preclinical and clinical investigations showed that the distribution of drugs is very heterogeneous within a given brain metastasis, despite the contrast enhancement in magnetic resonance imaging...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29307345/regulation-of-signal-transduction-cascades-by-pterostilbenes-in-different-cancers-is-it-a-death-knell-for-oncogenic-pathways
#11
Ghazala Butt, Rukset Attar, Sobia Tabassum, Aliye Aras, Muhammad Imran Qadir, Ulku Ozbey, Nada Alaaeddine, Beraat Ozcelik, Ammad Ahmad Farooqi
Interdisciplinary research has revolutionized the field of medicine and we have witnessed exponential increase in the high-impact research in past few decades. However, the road to this burgeoning research field is obstacle-ridden because of intratumor heterogeneity, loss of apoptosis and dysregulation of spatio-temporally controlled signaling pathways. Ground-breaking findings obtained through genetic, genomic and proteomic studies have considerably improved our concepts related to the complexity of protein network and excitingly, discovery of miRNAs has added another layer of intricacy to quantitatively regulated gene networks...
December 15, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29303928/endometrial-adenocarcinomas-with-significant-mucinous-differentiation-a-characterization-of-intratumoral-heterogeneity-of-kras-mutations-in-mucinous-and-endometrioid-histologic-components
#12
Cynthia L Jackson, Steven Hang, Katrine Hansen, Mai He, C James Sung, M Ruhul Quddus, Michelle Xiong, Yihong Wang, Nimesh R Patel, W Dwayne Lawrence, Jinjun Xiong
OBJECTIVE: KRAS mutations are frequently seen in malignancies with mucinous morphology. In our previous study, mucinous endometrial carcinomas were associated with a significantly higher frequency of KRAS mutations as compared with matched conventional endometrioid carcinomas. This study expands our previous report by exploring possible intratumoral heterogeneity for KRAS gene mutations in the mucinous components of mucinous carcinomas (MCs) and endometrioid carcinomas with significant mucinous differentiation (ECSMD) versus their associated "usual" endometrioid components...
January 4, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29303512/the-significance-of-intertumor-and-intratumor-heterogeneity-in-liver-cancer
#13
REVIEW
Jinping Liu, Hien Dang, Xin Wei Wang
Genomic analyses of primary liver cancer samples reveal a complex mutational landscape with vast intertumor and intratumor heterogeneity. Different primary liver tumors and subclones within each tumor display striking molecular and biological variations. Consequently, tumor molecular heterogeneity contributes to drug resistance and tumor relapse following therapy, which poses a substantial obstruction to improving outcomes of patients with liver cancer. There is an urgent need to the compositional and functional understanding of tumor heterogeneity...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29276709/tumor-heterogeneity-in-breast-cancer
#14
REVIEW
Gulisa Turashvili, Edi Brogi
Breast cancer is a heterogeneous disease and differs greatly among different patients (intertumor heterogeneity) and even within each individual tumor (intratumor heterogeneity). Clinical and morphologic intertumor heterogeneity is reflected by staging systems and histopathologic classification of breast cancer. Heterogeneity in the expression of established prognostic and predictive biomarkers, hormone receptors, and human epidermal growth factor receptor 2 oncoprotein is the basis for targeted treatment. Molecular classifications are indicators of genetic tumor heterogeneity, which is probed with multigene assays and can lead to improved stratification into low- and high-risk groups for personalized therapy...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29250210/quantification-of-multiple-tumor-clones-using-gene-array-and-sequencing-data
#15
Yichen Cheng, James Y Dai, Thomas G Paulson, Xiaoyu Wang, Xiaohong Li, Brian J Reid, Charles Kooperberg
Cancer development is driven by genomic alterations, including copy number aberrations. The detection of copy number aberrations in tumor cells is often complicated by possible contamination of normal stromal cells in tumor samples and intratumor heterogeneity, namely the presence of multiple clones of tumor cells. In order to correctly quantify copy number aberrations, it is critical to successfully de-convolute the complex structure of the genetic information from tumor samples. In this article, we propose a general Bayesian method for estimating copy number aberrations when there are normal cells and potentially more than one tumor clones...
June 2017: Annals of Applied Statistics
https://www.readbyqxmd.com/read/29245896/metabolomic-mapping-of-cancer-stem-cells-for-reducing-and-exploiting-tumor-heterogeneity
#16
Elisabet Cuyàs, Sara Verdura, Salvador Fernández-Arroyo, Joaquim Bosch-Barrera, Begoña Martin-Castillo, Jorge Joven, Javier A Menendez
Personalized cancer medicine based on the analysis of tumors en masse is limited by tumor heterogeneity, which has become a major obstacle to effective cancer treatment. Cancer stem cells (CSC) are emerging as key drivers of inter- and intratumoral heterogeneity. CSC have unique metabolic dependencies that are required not only for specific bioenergetic/biosynthetic demands but also for sustaining their operational epigenetic traits, i.e. self-renewal, tumor-initiation, and plasticity. Given that the metabolome is the final downstream product of all the -omic layers and, therefore, most representative of the biological phenotype, we here propose that a novel approach to better understand the complexity of tumor heterogeneity is by mapping and cataloging small numbers of CSC metabolomic phenotypes...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29244136/order-in-chaos-understanding-intratumoral-heterogeneity-in-gliomas-by-tracking-tumor-cell-fate
#17
Matei A Banu, Guy M McKhann
No abstract text is available yet for this article.
January 1, 2018: Neurosurgery
https://www.readbyqxmd.com/read/29233603/individual-susceptibility-analysis-using-patient-derived-slice-cultures-of-colorectal-carcinoma
#18
Rasmus Sönnichsen, Laura Hennig, Vera Blaschke, Karsten Winter, Justus Körfer, Susann Hähnel, Astrid Monecke, Christian Wittekind, Boris Jansen-Winkeln, René Thieme, Ines Gockel, Kerstin Grosser, Arved Weimann, Christoph Kubick, Volker Wiechmann, Achim Aigner, Ingo Bechmann, Florian Lordick, Sonja Kallendrusch
BACKGROUND: Nonresponse to chemotherapy in colorectal carcinoma (CRC) is still a clinical problem. For most established treatment regimens, no predictive biomarkers are available. Patient-derived tumor slice culture may be a promising ex vivo technology to assess the drug susceptibility in individual tumors. METHODS: Patient-derived slice cultures of CRC specimens were prepared according to a standardized protocol and treated with different concentrations of 5-fluorouracil (5-FU) and an adapted FOLFOX regimen (5-FU and oxaliplatin) to investigate histologic response...
November 21, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29228707/pd-l1-immunohistochemical-assays-for-assessment-of-therapeutic-strategies-involving-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-a-comparative-study
#19
Hyojin Kim, Hyun Jung Kwon, Soo Young Park, Eunhyang Park, Jin-Haeng Chung
Although immune checkpoints inhibitors have exhibited promising activity in clinical trials in non-small cell lung cancer (NSCLC) patients, the current programmed cell death-ligand 1 (PD-L1) assays are inconsistent in terms of the staining analysis and scoring system used. To verify the interchangeability of the available PD-L1 assays, we performed immunohistochemistry using three antibody clones used in clinical trials (22C3, SP263, and SP142) and the E1L3N clone as a laboratory developed test for 97 resected NSCLC specimens...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228656/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#20
Stefanie Avril, Yasemin Dincer, Katharina Malinowsky, Claudia Wolff, Sibylle Gündisch, Alexander Hapfelmeier, Melanie Boxberg, Holger Bronger, Karl-Friedrich Becker, Barbara Schmalfeldt
Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response. 192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity...
November 17, 2017: Oncotarget
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