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intratumor heterogeneity

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https://www.readbyqxmd.com/read/28650485/neuroblastoma-is-composed-of-two-super-enhancer-associated-differentiation-states
#1
Tim van Groningen, Jan Koster, Linda J Valentijn, Danny A Zwijnenburg, Nurdan Akogul, Nancy E Hasselt, Marloes Broekmans, Franciska Haneveld, Natalia E Nowakowska, Johannes Bras, Carel J M van Noesel, Aldo Jongejan, Antoine H van Kampen, Linda Koster, Frank Baas, Lianne van Dijk-Kerkhoven, Margriet Huizer-Smit, Maria C Lecca, Alvin Chan, Arjan Lakeman, Piet Molenaar, Richard Volckmann, Ellen M Westerhout, Mohamed Hamdi, Peter G van Sluis, Marli E Ebus, Jan J Molenaar, Godelieve A Tytgat, Bart A Westerman, Johan van Nes, Rogier Versteeg
Neuroblastoma and other pediatric tumors show a paucity of gene mutations, which has sparked an interest in their epigenetic regulation. Several tumor types include phenotypically divergent cells, resembling cells from different lineage development stages. It has been proposed that super-enhancer-associated transcription factor (TF) networks underlie lineage identity, but the role of these enhancers in intratumoral heterogeneity is unknown. Here we show that most neuroblastomas include two types of tumor cells with divergent gene expression profiles...
June 26, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28645942/mutational-heterogeneity-in-apc-and-kras-arises-at-the-crypt-level-and%C3%A2-leads-to-polyclonality-in-early-colorectal-tumorigenesis
#2
Mireia Gausachs, Ester Borras, Kyle Chang, Sara González, Daniel Azuara, Axel Delgado Amador, Adriana Lopez-Doriga, F Anthony San Lucas, Xavier Sanjuan, Maria jOSE Paules, Melissa Taggart, Gareth Davies, Erik A Ehli, Jerry Fowler, Victor Moreno, Marta Pineda, Y Nancy You, Patrick M Lynch, Conxi Lazaro, Nicholas E Navin, Paul Scheet, Ernest T Hawk, Gabriel Capella, Eduardo Vilar
Purpose:  The majority of genomic alterations causing intratumoral heterogeneity (ITH) in colorectal cancer (CRC) are thought to arise during early stages of carcinogenesis as a burst but only after truncal mutations in APC have expanded a single founder clone. We have investigated if the initial source of ITH is consequent to multiple independent lineages derived from different crypts harboring distinct truncal APC and driver KRAS mutations, thus challenging the prevailing monoclonal monocryptal model. <p>Experimental design: High-depth next-generation sequencing and SNP arrays were performed in whole lesion extracts of 37 FAP colorectal adenomas...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645214/sodium-fluorescein-facilitates-guided-sampling-of-diagnostic-tumor-tissue-in-nonenhancing-gliomas
#3
Stephen G Bowden, Justin A Neira, Brian J A Gill, Timothy H Ung, Zachary K Englander, George Zanazzi, Peter D Chang, Jorge Samanamud, Jack Grinband, Sameer A Sheth, Guy M McKhann, Michael B Sisti, Peter Canoll, Randy S D'Amico, Jeffrey N Bruce
BACKGROUND: Accurate tissue sampling in nonenhancing (NE) gliomas is a unique surgical challenge due to their intratumoral histological heterogeneity and absence of contrast enhancement as a guide for intraoperative stereotactic guidance. Instead, T2/fluid-attenuated inversion-recovery (FLAIR) hyperintensity on MRI is commonly used as an imaging surrogate for pathological tissue, but sampling from this region can yield nondiagnostic or underdiagnostic brain tissue. Sodium fluorescein is an intraoperative fluorescent dye that has a high predictive value for tumor identification in areas of contrast enhancement and NE in glioblastomas...
June 21, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28640708/medulloblastoma-from-myth-to-molecular
#4
Vijay Ramaswamy, Michael D Taylor
Current therapies for medulloblastoma were introduced primarily in the 1980s and consist of predominantly cytotoxic, nontargeted approaches. Mortality from medulloblastoma remains significant. In addition, many survivors suffer from severe treatment-related effects of radiation and cytotoxic chemotherapy. Further intensification of nonspecific therapy is unlikely to offer additional benefits, because survival rates have reached a plateau. Recent publications in medulloblastoma have revolved largely around the recognition that medulloblastoma per se does not exist, but rather, that there are a group of histologically similar but clinically and molecularly distinct entities that have been grouped under that rubric...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28639131/mirna-signature-of-hepatocellular-carcinoma-vascularization-how-the-controls-can-influence-the-signature
#5
Silvia Fittipaldi, Francesco Vasuri, Sonia Bonora, Alessio Degiovanni, Giacomo Santandrea, Alessandro Cucchetti, Laura Gramantieri, Luigi Bolondi, Antonia D'Errico
BACKGROUND: miRNA deregulation and vascular modifications constitute promising predictors in the study of hepatocellular carcinoma (HCC). In the literature, the relative miRNA abundance in HCC is usually determined using as control non-matched tumoral tissue, healthy liver, or cirrhotic liver. However, a common standard RNA control for the normalization toward the tissue gene expression was not settled yet. AIM: To assess the differences existing in the quantitative miRNA gene expression in HCC on tissue according to two different liver controls...
June 21, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28635565/prostate-cancer-stem-cells-from-theory-to-practice
#6
Jan Adamowicz, Katayoon Pakravan, Babak Bakhshinejad, Tomasz Drewa, Sadegh Babashah
None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease...
February 7, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28633165/investigation-of-biotransport-in-a-tumor-with-uncertain-material-properties-using-a-non-intrusive-spectral-uncertainty-quantification-method
#7
Alen Alexanderian, Liang Zhu, Maher Salloum, Ronghui Ma, Meilin Yu
In this study, statistical models are developed for modeling uncertain heterogeneous permeability and porosity in tumors, and the resulting uncertainties in pressure and velocity fields during an intratumoral injection are quantified using a non-intrusive spectral uncertainty quantification (UQ) method. Specifically, the uncertain permeability is modeled as a log-Gaussian random field, represented using a truncated Karhunen-Loeve (KL) expansion, and the uncertain porosity is modeled as a log-normal random variable...
June 20, 2017: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/28622685/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#8
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...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28616310/intratumoral-heterogeneity-of-esophageal-squamous-cell-carcinoma
#9
EDITORIAL
Dirk Walter
No abstract text is available yet for this article.
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28615538/expression-of-lag-3-defines-exhaustion-of-intratumoral-pd-1-t-cells-and-correlates-with-poor-outcome-in-follicular-lymphoma
#10
Zhi-Zhang Yang, Hyo Jin Kim, Jose C Villasboas, Ya-Ping Chen, Tammy Price-Troska, Shahrzad Jalali, Mara Wilson, Anne J Novak, Stephen M Ansell
Exhausted T-cells in follicular lymphoma (FL) typically express PD-1, but expression of PD-1 is not limited to exhausted cells. Although expected to be functionally suppressed, we found that the population of intratumoral PD-1+ T cells were predominantly responsible for production of cytokines and granules. This surprising finding prompted us to explore the involvement of LAG-3 to specifically identify functionally exhausted T cells. We found that LAG-3 was expressed on a subset of intratumoral T cells from FL and LAG-3+ T cells almost exclusively came from PD-1+ population...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614814/tumor-heterogeneity-in-endometrial-carcinoma-practical-consequences
#11
Sònia Gatius, Dolors Cuevas, Carlos Fernández, Berta Roman-Canal, Virginia Adamoli, Josep Maria Piulats, Núria Eritja, Mireia Martin-Satue, Gema Moreno-Bueno, Xavier Matias-Guiu
Endometrial carcinoma (EC) shows intertumor heterogeneity, with several different histologic types differing in their morphologic and molecular features. There is also intratumoral morphologic heterogeneity, with different neoplastic cell components within the same tumor, with different morphologic and molecular features. In this article, we discuss the consequences of tumor heterogeneity in EC at the morphologic and molecular levels, by describing some illustrative examples produced by the research team. They are (1) morphologic heterogeneity in conventional EC and mixed tumors, (2) EC with microsatellite instability, (3) branched evolution as shown by exome sequencing analysis, (4) morphologic, molecular, and metabolomic differences between the tumor surface and myometrial invasion front, (5) tumor heterogeneity at the microenviromental level, (6) the sensitivity of endometrial aspirates to detect tumor heterogeneity in EC, and (7) sampling strategies to detect tumor heterogeneity in hysterectomy specimens...
June 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28611289/next-generation-sequencing-and-molecular-imaging-identify-egfr-mutation-and-amplification-in-a-glioblastoma-multiforme-patient-treated-with-an-egfr-inhibitor-a-case-report
#12
Ke Zhou, Hui Yao, Xuewen Zhang, Jiangang Liu, Zhenyu Qi, Xueshun Xie, Xiaoting Xu, Youxin Zhou, Zhengquan Yu, Zhong Wang, Yanjun Che, Yulun Huang
Epidermal growth factor receptor (EGFR) mutations and amplifications are frequently reported in glioblastoma multiforme (GBM) patients. In this case report, we utilize next-generation sequencing (NGS) and EGFR molecular imaging to investigate intratumoral heterogeneity in a male patient presenting with GBM. Further, we describe the patient's clinical course as well as outcomes of targeted EGFR therapy with erlotinib, an EGFR tyrosine kinase inhibitor (TKI). NGS demonstrated the presence of an EGFR mutation and amplification in our patient...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605656/metabolism-shapes-the-tumor-microenvironment
#13
REVIEW
Miguel Reina-Campos, Jorge Moscat, Maria Diaz-Meco
Tumors are strongly influenced by the surrounding normal tissue, which forms a specialized niche termed the tumor microenvironment (TME). The TME is modeled by cancer cells for their own benefit through a complex array of interactions. The identification of new forms of communication within the TME, which are dependent on the tumor's metabolic activity, has expanded our understanding of this heterocellular regulation and has revealed potential therapeutic targets. This review will summarize recent findings on the metabolic regulation of tumor cells by the TME...
June 9, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28601576/real-time-monitoring-of-microdistribution-of-antibody-photon-absorber-conjugates-during-photoimmunotherapy-in-vivo
#14
Qinggong Tang, Tadanobu Nagaya, Yi Liu, Jonathan Lin, Kazuhide Sato, Hisataka Kobayashi, Yu Chen
Photoimmunotherapy (PIT) is an emerging low side effect cancer therapy based on a monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye IRDye 700DX. IR700 is fluorescent, can be used as an imaging agent, and also is phototoxic. It induces rapid cell death after exposure to NIR light. PIT induces highly selective cancer cell death, while leaving most of tumor blood vessels unharmed, leading to an effect called super-enhanced permeability and retention (SUPR). SUPR significantly improves the effectiveness of the anticancer drug...
June 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28591736/clinically-relevant-morphological-structures-in-breast-cancer-represent-transcriptionally-distinct-tumor-cell-populations-with-varied-degrees-of-epithelial-mesenchymal-transition-and-cd44-cd24-stemness
#15
Evgeny V Denisov, Nikolay A Skryabin, Tatiana S Gerashchenko, Lubov A Tashireva, Jochen Wilhelm, Mikhail A Buldakov, Aleksei A Sleptcov, Igor N Lebedev, Sergey V Vtorushin, Marina V Zavyalova, Nadezhda V Cherdyntseva, Vladimir M Perelmuter
Intratumor morphological heterogeneity in breast cancer is represented by different morphological structures (tubular, alveolar, solid, trabecular, and discrete) and contributes to poor prognosis; however, the mechanisms involved remain unclear. In this study, we performed 3D imaging, laser microdissection-assisted array comparative genomic hybridization and gene expression microarray analysis of different morphological structures and examined their association with the standard immunohistochemistry scorings and CD44+CD24- cancer stem cells...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586758/notch-signaling-regulates-metabolic-heterogeneity-in-glioblastoma-stem-cells
#16
N Sumru Bayin, Joshua D Frenster, Rajeev Sen, Sheng Si, Aram S Modrek, Nataliya Galifianakis, Igor Dolgalev, Valerio Ortenzi, Irineu Illa-Bochaca, Anadjeet Khahera, Jonathan Serrano, Luis Chiriboga, David Zagzag, John G Golfinos, Werner Doyle, Aristotelis Tsirigos, Adriana Heguy, Mitch Chesler, Mary Helen Barcellos-Hoff, Matija Snuderl, Dimitris G Placantonakis
Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular microenvironments within tumors. The molecular mechanisms that allow GSCs to occupy such contrasting niches are not understood. We used patient-derived GBM cultures to identify GSC subtypes with differential activation of Notch signaling, which co-exist in tumors but occupy distinct niches and match their metabolism accordingly. Multipotent GSCs with Notch pathway activation reside in perivascular niches, and are unable to entrain anaerobic glycolysis during hypoxia...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28582348/phenotypic-intratumoral-heterogeneity-of-endometrial-carcinomas
#17
Cátia Silva, Ana S Pires-Luís, Eduardo Rocha, Carla Bartosch, José M Lopes
Intratumoral heterogeneity has been shown to play an important role in diagnostic accuracy, development of treatment resistance, and prognosis of cancer patients. Recent studies have proposed quantitative measurement of phenotypic intratumoral heterogeneity, but no study is yet available in endometrial carcinomas. In our study we evaluated the phenotypic intratumoral heterogeneity of a consecutive series of 10 endometrial carcinomas using measures of dispersion and diversity. Morphometric architectural (%tumor cells, %solid tumor, %differentiated tumor, and %lumens) and nuclear [volume-weighted mean nuclear volume (ν¯v)] parameters, as well as estrogen receptor, progesterone receptor, p53, vimentin, and beta-catenin immunoexpression (H-score) were digitally analyzed in 20 microscopic fields per carcinoma...
June 2, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28581516/pancreatic-cancer-heterogeneity-and-response-to-mek-inhibition
#18
K Pedersen, F Bilal, C Bernadó Morales, M T Salcedo, T Macarulla, D Massó-Vallés, V Mohan, A Vivancos, M-J Carreras, X Serres, M Abu-Suboh, J Balsells, E Allende, I Sagi, L Soucek, J Tabernero, J Arribas
Our increasing knowledge of the mechanisms behind the progression of pancreatic cancer (PC) has not yet translated into effective treatments. Many promising drugs have failed in the clinic, highlighting the need for better preclinical models to assess drug efficacy and characterize mechanisms of resistance. Using different experimental models, including patient-derived xenografts (PDXs), we gauged the efficacy of therapies aimed at two hallmark lesions of PCs: activation of signaling pathways by oncogenic KRAS and inactivation of tumor-suppressor genes...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28581503/between-region-genetic-divergence-reflects-the-mode-and-tempo-of-tumor-evolution
#19
Ruping Sun, Zheng Hu, Andrea Sottoriva, Trevor A Graham, Arbel Harpak, Zhicheng Ma, Jared M Fischer, Darryl Shibata, Christina Curtis
Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural selection within established human tumors are lacking. By simulating spatial tumor growth under different evolutionary modes and examining patterns of between-region subclonal genetic divergence from multiregion sequencing (MRS) data, we demonstrate that it is feasible to distinguish tumors driven by strong positive subclonal selection from those evolving neutrally or under weak selection, as the latter fail to dramatically alter subclonal composition...
June 5, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28574839/advances-in-single-cell-rna-sequencing-and-its-applications-in-cancer-research
#20
REVIEW
Sibo Zhu, Tao Qing, Yuanting Zheng, Li Jin, Leming Shi
Unlike population-level approaches, single-cell RNA sequencing enables transcriptomic analysis of an individual cell. Through the combination of high-throughput sequencing and bioinformatic tools, single-cell RNA-seq can detect more than 10,000 transcripts in one cell to distinguish cell subsets and dynamic cellular changes. After several years' development, single-cell RNA-seq can now achieve massively parallel, full-length mRNA sequencing as well as in situ sequencing and even has potential for multi-omic detection...
May 16, 2017: Oncotarget
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