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intratumor heterogeneity

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https://www.readbyqxmd.com/read/28432052/genomic-instability-in-cancer-teetering-on-the-limit-of-tolerance
#1
REVIEW
Noemi Andor, Carlo C Maley, Hanlee P Ji
Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold...
April 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428887/differential-intratumoral-distributions-of-cd8-and-cd163-immune-cells-as-prognostic-biomarkers-in-breast-cancer
#2
Sotirios P Fortis, Michael Sofopoulos, Nectaria N Sotiriadou, Christoforos Haritos, Christoforos K Vaxevanis, Eleftheria A Anastasopoulou, Nicole Janssen, Niki Arnogiannaki, Alexandros Ardavanis, Graham Pawelec, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Tumor immune cell infiltrates are essential in hindering cancer progression and may complement the TNM classification. CD8+ and CD163+ cells have prognostic impact in breast cancer but their spatial heterogeneity has not been extensively explored in this type of cancer. Here, their potential as prognostic biomarkers was evaluated, depending on their combined densities in the tumor center (TC) and the tumor invasive margin (IM). METHODS: CD8+ and CD163+ cells were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from a cohort totaling 162 patients with histologically-confirmed primary invasive non-metastatic ductal breast cancer diagnosed between 2000 and 2015...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28423542/dna-methylation-intratumor-heterogeneity-in-localized-lung-adenocarcinomas
#3
Kelly Quek, Jun Li, Marcos Estecio, Jiexin Zhang, Junya Fujimoto, Emily Roarty, Latasha Little, Chi-Wan Chow, Xingzhi Song, Carmen Behrens, Taiping Chen, William N William, Stephen Swisher, John Heymach, Ignacio Wistuba, Jianhua Zhang, Andrew Futreal, Jianjun Zhang
Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#4
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420318/advancing-clinicopathologic-diagnosis-of-high-risk-neuroblastoma-using-computerized-image-analysis-and-proteomic-profiling
#5
M Khalid Khan Niazi, Jonathan H Chung, Katherine J Heaton-Johnson, Daniel Martinez, Raquel Castellanos, Meredith S Irwin, Stephen R Master, Bruce R Pawel, Metin N Gurcan, Daniel A Weiser
A subset of patients with neuroblastoma are at extremely high risk for treatment failure, though they are not identifiable at diagnosis and therefore have the highest mortality with conventional treatment approaches. Despite tremendous understanding of clinical and biological features that correlate with prognosis, neuroblastoma at ultra-high risk for treatment failure remains a diagnostic challenge. As a first step towards improving prognostic risk stratification within the high-risk group of patients, we determined the feasibility of using computerized image analysis and proteomic profiling on single slides from diagnostic tissue specimens...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28419182/molecular-classification-of-pulmonary-sarcomatoid-carcinomas-suggests-new-therapeutic-opportunities
#6
N Pécuchet, T Vieira, N Rabbe, M Antoine, H Blons, J Cadranel, P Laurent-Puig, M Wislez
Background: Pulmonary sarcomatoid carcinoma (SC) is a rare disease with poor prognosis and with strong inter- and intratumor heterogeneity. However, molecular classification is currently focused on activating MET mutations. We sought to better characterize the molecular diversity of SC using mutational signatures that reflect different mutational processes, such as tobacco-associated adducts (signature 4), BRCA1/BRCA2 deficiency (signature 3) or APOBEC enzyme deamination (signatures 2&13)...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28416949/circulating-tumor-dna-in-a-breast-cancer-patient-s-plasma-represents-driver-alterations-in-the-tumor-tissue
#7
Jieun Lee, Sung-Min Cho, Min Sung Kim, Sug Hyung Lee, Yeun-Jun Chung, Seung-Hyun Jung
Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28412735/glucose-deprivation-elicits-phenotypic-plasticity-via-zeb1-mediated-expression-of-nnmt
#8
Justyna Kanska, Paul-Joseph P Aspuria, Barbie Taylor-Harding, Lindsay Spurka, Vincent Funari, Sandra Orsulic, Beth Y Karlan, W Ruprecht Wiedemeyer
Glucose is considered the primary energy source for all cells, and some cancers are addicted to glucose. Here, we investigated the functional consequences of chronic glucose deprivation in serous ovarian cancer cells. We found that cells resistant to glucose starvation (glucose-restricted cells) demonstrated increased metabolic plasticity that was dependent on NNMT (Nicotinamide N-methyltransferase) expression. We further show that ZEB1 induced NNMT, rendered cells resistant to glucose deprivation and recapitulated metabolic adaptations and mesenchymal gene expression observed in glucose-restricted cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411844/research-techniques-made-simple-mass-cytometry%C3%A2-analysis-tools-for-decrypting-the%C3%A2-complexity%C3%A2-of-biological-systems
#9
Tiago R Matos, Hongye Liu, Jerome Ritz
Mass cytometry by time-of-flight experiments allow analysis of over 40 functional and phenotypic cellular markers simultaneously at the single-cell level. The data dimensionality escalation accentuates limitations, inherent to manual analysis, as being subjective, labor-intensive, slow, and often incapable of showing the detailed features of each unique cell within populations. The subsequent challenge of examining, visualizing, and presenting mass cytometry data has motivated continuous development of dimensionality reduction methods...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28408240/intratumor-heterogeneity-in-primary-kidney-cancer-revealed-by-metabolic-profiling-of-multiple-spatially-separated-samples-within-tumors
#10
Takatsugu Okegawa, Megumi Morimoto, Satoru Nishizawa, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Toshiya Tamura, Ayumi Ando, Yoshinori Satomi, Kikuo Nutahara, Takahito Hara
Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant pathways in kidney cancer are elevated, with frequent mutation of the VHL gene. Intratumor genetic heterogeneity has been recently demonstrated in kidney cancer. However, intratumor metabolic heterogeneity has not been investigated. Here, we used global metabolomics analysis and tissue slice tracer studies to demonstrate that different portions of a human primary kidney tumor possess different metabolic characteristics and drug sensitivity...
April 6, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28407030/intratumoral-heterogeneity-pathways-to-treatment-resistance-and-relapse-in-human-glioblastoma
#11
M A Qazi, P Vora, C Venugopal, S S Sidhu, J Moffat, C Swanton, S K Singh
Intratumoral heterogeneity (ITH) has increasingly being described for multiple cancers as the root cause of therapy resistance. Recent studies have started to explore the scope of ITH in glioblastoma (GBM), a highly aggressive and fatal form of brain tumor, to explain its inevitable therapy resistance and disease relapse. In this review, we detail the emerging data that explores the extensive genetic, cellular and functional ITH present in GBM. We discuss current experimental models of human GBM recurrence and suggest harnessing new technologies (CRISPR-Cas9 screening, CyTOF, cellular barcoding, single cell analysis) to delineate GBM ITH and identify treatment-refractory cell populations, thus opening new therapeutic windows...
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28405764/prognostic-implication-of-cd274-pd-l1-protein-expression-in-tumor-infiltrating-immune-cells-for-microsatellite-unstable-and-stable-colorectal-cancer
#12
Kyu Sang Lee, Yoonjin Kwak, Soyeon Ahn, Eun Shin, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC...
April 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28400153/spatiotemporal-diversification-of-intrapatient-genomic-clones-and-early-drug-development-concepts-realize-the-roadmap-of-precision-cancer-medicine
#13
REVIEW
Dimitrios H Roukos
The unmet clinical needs of high relapse and cancer-related death rates are reflected by the poor understanding of the genome-wide mutational landscape and molecular mechanisms orchestrating therapeutic resistance. Emerging potential solutions to this challenge include the exploration of cancer genome dynamic evolution in time and space. Breakthrough next-generation sequencing (NGS) applications including multiregional NGS for intratumor heterogeneity identification, repeated cell-free DNA/circulating tumor DNA-NGS for detecting circulating genomic subclones and their comparison to reveal intrapatient heterogeneity (IPH) could identify the dynamic emergence of resistant subclones in the neoadjuvant, adjuvant and metastatic setting...
April 8, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28392802/capturing-genomic-evolution-of-lung-cancers-through-liquid-biopsy-for-circulating-tumor-dna
#14
REVIEW
Michael Offin, Jacob J Chabon, Pedram Razavi, James M Isbell, Charles M Rudin, Maximilian Diehn, Bob T Li
Genetic sequencing of malignancies has become increasingly important to uncover therapeutic targets and capture the tumor's dynamic changes to drug sensitivity and resistance through genomic evolution. In lung cancers, the current standard of tissue biopsy at the time of diagnosis and progression is not always feasible or practical and may underestimate intratumoral heterogeneity. Technological advances in genetic sequencing have enabled the use of circulating tumor DNA (ctDNA) analysis to obtain information on both targetable mutations and capturing real-time Darwinian evolution of tumor clones and drug resistance mechanisms under selective therapeutic pressure...
2017: Journal of Oncology
https://www.readbyqxmd.com/read/28390874/application-of-single-cell-technology-in-cancer-research
#15
REVIEW
Shao-Bo Liang, Li-Wu Fu
In this review, we have outlined the application of single-cell technology in cancer research. Single-cell technology has made encouraging progress in recent years and now provides the means to detect rare cancer cells such as circulating tumor cells and cancer stem cells. We reveal how this technology has advanced the analysis of intratumor heterogeneity and tumor epigenetics, and guided individualized treatment strategies. The future prospects now are to bring single-cell technology into the clinical arena...
April 5, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28389596/single-cell-analysis-of-circulating-tumor-cells-as-a-window-into-tumor-heterogeneity
#16
David T Miyamoto, David T Ting, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber
Recent advances in microfluidic approaches have enabled the efficient isolation and detailed molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of patients with cancer. Single-cell molecular analyses of CTCs reveal a tremendous degree of intracellular heterogeneity in CTC populations, reflective of heterogeneity across different patients as well as the underlying heterogeneity of tumors within each individual patient. These studies have enabled the identification of heterogeneous drug resistance mechanisms that can coexist in treatment refractory tumors...
April 7, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28381438/modeling-breast-cancer-intertumor-and-intratumor-heterogeneity-using-xenografts
#17
Alejandra Bruna, Oscar M Rueda, Carlos Caldas
Breast cancer is a heterogeneous disease that can be stratified in at least 10 different subtypes. We present here a platform for derivation of preclinical models based on patient-derived tumor xenografts (PDTXs) that represent these subgroups. These models preserve the transcriptome, methylome, copy-number, and mutational landscape features of the tumor of origin through different passaging. Furthermore, the intratumoral composition of these models is formed by communities of clones very similar to the ones present in the originating tumor...
April 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28379574/the-role-of-angiogenesis-in-group-3-medulloblastoma-pathogenesis-and-survival
#18
Eric M Thompson, Stephen T Keir, Talaignair Venkatraman, Christopher Lascola, Kristen W Yeom, Andrew B Nixon, Yingmiao Liu, Daniel Picard, Marc Remke, Darell D Bigner, Vijay Ramaswamy, Michael D Taylor
Background: Of the 4 medulloblastoma subgroups, Group 3 is the most aggressive but the importance of angiogenesis is unknown. This study sought to determine the role of angiogenesis and identify clinically relevant biomarkers of tumor vascularity and survival in Group 3 medulloblastoma. Methods: VEGFA mRNA expression and survival from several patient cohorts were analyzed. Group 3 xenografts were implanted intracranially in nude rats. Dynamic susceptibility weighted (DSC) MRI and susceptibility weighted imaging (SWI) were obtained...
April 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28376920/molecular-clonality-analysis-of-esophageal-adenocarcinoma-by-multiregion-sequencing-of-tumor-samples
#19
Anna M J van Nistelrooij, Ronald van Marion, Linetta B Koppert, Katharina Biermann, Manon C W Spaander, Hugo W Tilanus, J Jan B van Lanschot, Bas P L Wijnhoven, Winand N M Dinjens
BACKGROUND: Intratumor heterogeneity has been demonstrated in several cancer types, following a model of branched evolution. It is unknown to which extent intratumor heterogeneity is applicable to esophageal adenocarcinoma. Therefore the aim of this study was to characterise intratumor heterogeneity in esophageal adenocarcinoma. METHODS: Multiregional targeted sequencing of four commonly altered genes was performed on 19 tumor regions collected from five esophageal adenocarcinomas...
April 4, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28376187/a-novel-diagnostic-tool-for-selecting-patients-with-mesenchymal-type-colon-cancer-reveals-intratumor-subtype-heterogeneity
#20
Inge Ubink, Sjoerd G Elias, Cathy B Moelans, Miangela M Laclé, Wilhelmina M U van Grevenstein, Paul J van Diest, Inne H M Borel Rinkes, Onno Kranenburg
Background: Consensus molecular subtype 4 (CMS4) is a recently identified aggressive colon cancer subtype for which platelet-derived growth factor receptors (PDGFRs) and KIT are potential therapeutic targets. We aimed to develop a clinically applicable CMS4 reverse transcription polymerase chain reaction (RT-qPCR) test to select patients for PDGFR/KIT-targeted therapy. Methods: We used logistic regression to develop a CMS4 prediction rule based on microarray expression values of PDGFRA , PDGFRB , PDGFC , and KIT (566 training and 1259 test samples, using the 273-gene random forest classifier as CMS4 reference standard)...
August 1, 2017: Journal of the National Cancer Institute
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