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Tumor heterogeneity

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https://www.readbyqxmd.com/read/27933753/mass-cytometry-of-follicular-lymphoma-tumors-reveals-intrinsic-heterogeneity-in-proteins-including-hla-dr-and-a-deficit-in-non-malignant-plasmablast-and-germinal-center-b-cell-populations
#1
Cara Ellen Wogsland, Allison Rae Greenplate, Arne Kolstad, June Helen Myklebust, Jonathan Michael Irish, Kanutte Huse
BACKGROUND: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the non-malignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity. METHODS: Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, non-malignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933281/pet-imaging-of-urokinase-type-plasminogen-activator-receptor-upar-in-prostate-cancer-current-status-and-future-perspectives
#2
REVIEW
Dorthe Skovgaard, Morten Persson, Andreas Kjaer
Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity...
2016: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27933061/ncr1-expression-identifies-canine-natural-killer-cell-subsets-with-phenotypic-similarity-to-human-natural-killer-cells
#3
Jennifer A Foltz, Srinivas S Somanchi, Yanwen Yang, Arianexys Aquino-Lopez, Erin E Bishop, Dean A Lee
Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46), the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27932568/targeting-hif2-in-clear-cell-renal-cell-carcinoma
#4
Hyejin Cho, William G Kaelin
Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1...
December 8, 2016: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/27932399/novel-hybrid-phenotype-revealed-in-small-cell-lung-cancer-by-a-transcription-factor-network-model-that-can-explain-tumor-heterogeneity
#5
Akshata R Udyavar, David J Wooten, Megan D Hoeksema, Mukesh Bansal, Andrea Califano, Lourdes Estrada, Santiago Schnell, Jonathan M Irish, Pierre P Massion, Vito Quaranta
Small cell lung cancer (SCLC) is a devastating disease due to its propensity for early invasion and refractory relapse after initial treatment response. Although these aggressive traits have been associated with phenotypic heterogeneity, our understanding of this association remains incomplete. To fill this knowledge gap, we inferred a set of 33 transcription factors (TF) associated with gene signatures of the known neuroendocrine/epithelial (NE) and non-neuroendocrine/mesenchymal-like (ML) SCLC phenotypes...
December 8, 2016: Cancer Research
https://www.readbyqxmd.com/read/27931250/tracing-the-origin-of-disseminated-tumor-cells-in-breast-cancer-using-single-cell-sequencing
#6
Jonas Demeulemeester, Parveen Kumar, Elen K Møller, Silje Nord, David C Wedge, April Peterson, Randi R Mathiesen, Renathe Fjelldal, Masoud Zamani Esteki, Koen Theunis, Elia Fernandez Gallardo, A Jason Grundstad, Elin Borgen, Lars O Baumbusch, Anne-Lise Børresen-Dale, Kevin P White, Vessela N Kristensen, Peter Van Loo, Thierry Voet, Bjørn Naume
BACKGROUND: Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. RESULTS: We sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients...
December 9, 2016: Genome Biology
https://www.readbyqxmd.com/read/27931038/heterogeneity-of-glucose-metabolism-in-esophageal-cancer-measured-by-fractal-analysis-of-fluorodeoxyglucose-positron-emission-tomography-image-correlation-between-metabolic-heterogeneity-and-survival
#7
Toru Tochigi, Kiyohiko Shuto, Tsuguaki Kono, Gaku Ohira, Takayuki Tohma, Hisashi Gunji, Koichi Hayano, Kazuo Narushima, Takeshi Fujishiro, Toshiharu Hanaoka, Yasunori Akutsu, Shinichi Okazumi, Hisahiro Matsubara
BACKGROUND: Intratumoral heterogeneity is a well-recognized characteristic feature of cancer. The purpose of this study is to assess the heterogeneity of the intratumoral glucose metabolism using fractal analysis, and evaluate its prognostic value in patients with esophageal squamous cell carcinoma (ESCC). METHODS: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies of 79 patients who received curative surgery were evaluated. FDG-PET images were analyzed using fractal analysis software, where differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor lesion...
December 9, 2016: Digestive Surgery
https://www.readbyqxmd.com/read/27930739/heterogeneity-in-comparisons-of-discontinuation-of-tumor-necrosis-factor-antagonists-in-rheumatoid-arthritis-a-meta-analysis
#8
Anat Fisher, Ken Bassett, Gautam Goel, Dana Stanely, M Alan Brookhart, Hugh R Freeman, James M Wright, Colin R Dormuth
OBJECTIVE: We did a systematic review of studies comparing discontinuation of tumor necrosis factor alpha (TNF) antagonists in rheumatoid arthritis (RA) patients, pooled hazard ratios and assessed clinical and methodological heterogeneity. METHODS: We searched MEDLINE and EMBASE until June 2015 for pairwise hazard ratios for discontinuing infliximab, etanercept, and adalimumab from cohorts of RA patients. Hazard ratios were pooled using inverse variance weighting and random effects estimates of the combined hazard ratio were obtained...
2016: PloS One
https://www.readbyqxmd.com/read/27930094/cancer-stem-cell-hypothesis-for-therapeutic-innovation-in-clinical-oncology-taking-the-root-out-not-chopping-the-leaf
#9
Kevin Dzobo, Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Lamech M Mwapagha, Nasir Al-Awwad, Collet Dandara, M Iqbal Parker
Clinical oncology is in need of therapeutic innovation. New hypotheses and concepts for translation of basic research to novel diagnostics and therapeutics are called for. In this context, the cancer stem cell (CSC) hypothesis rests on the premise that tumors comprise tumor cells and a subset of tumor-initiating cells, CSCs, in a quiescent state characterized by slow cell cycling and expression of specific stem cell surface markers with the capability to maintain a tumor in vivo. The CSCs have unlimited self-renewal abilities and propagate tumors through division into asymmetric daughter cells...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27929800/harnessing-benefit-from-targeting-tumor-associated-carbohydrate-antigens
#10
Thomas Kieber-Emmons, Bejatohlah Monzavi-Karbassi, Laura F Hutchins, Angela Pennisi, Issam Makhoul
Integrating additive or synergistic antitumor effects that focus on distinct elements of tumor biology are the most rational strategies for cancer treatment. Treatments for breast cancer have increased overall survival, but remain limited by lack of efficacy in a subset of breast cancer patients. The real challenge is to define what elements of tumor biology make the most sense to be integrated. An emerging strategy is to consider a systems biology approach to impact multiple interactions in networks as compared to hitting a specific protein-protein interaction target...
December 8, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27929582/liquid-biopsy-on-chip-a-paradigm-shift-towards-the-understanding-of-cancer-metastasis
#11
REVIEW
Amogha Tadimety, Abeer Syed, Yuan Nie, Christina R Long, Kasia M Kready, John X J Zhang
This comprehensive review serves as a guide for developing scalable and robust liquid biopsies on chip for capture, detection, and analysis of circulating tumor cells (CTCs). Liquid biopsy, the detection of biomarkers from body fluids, has proven challenging because of CTC rarity and the heterogeneity of CTCs shed from tumors. The review starts with the underlying biological mechanisms that make liquid biopsy a challenge before moving into an evaluation of current technological progress. Then, a framework for evaluation of the technologies is presented with special attention to throughput, capture rate, and cell viability for analysis...
December 8, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/27929496/experimental-evaluation-of-a-gpu-based-monte-carlo-dose-calculation-algorithm-in-the-monaco-treatment-planning-system
#12
Moti R Paudel, Anthony Kim, Arman Sarfehnia, Sayed B Ahmad, David J Beachey, Arjun Sahgal, Brian M Keller
A new GPU-based Monte Carlo dose calculation algorithm (GPUMCD), devel-oped by the vendor Elekta for the Monaco treatment planning system (TPS), is capable of modeling dose for both a standard linear accelerator and an Elekta MRI linear accelerator. We have experimentally evaluated this algorithm for a standard Elekta Agility linear accelerator. A beam model was developed in the Monaco TPS (research version 5.09.06) using the commissioned beam data for a 6 MV Agility linac. A heterogeneous phantom representing several scenarios - tumor-in-lung, lung, and bone-in-tissue - was designed and built...
November 8, 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/27929464/labeling-of-breast-cancer-patient-derived-xenografts-with-traceable-reporters-for-tumor-growth-and-metastasis-studies
#13
Colton Hanna, Letty Kwok, Jessica Finlay-Schultz, Carol A Sartorius, Diana M Cittelly
The use of preclinical models to study tumor biology and response to treatment is central to cancer research. Long-established human cell lines, and many transgenic mouse models, often fail to recapitulate the key aspects of human malignancies. Thus, alternative models that better represent the heterogeneity of patients' tumors and their metastases are being developed. Patient-derived xenograft (PDX) models in which surgically resected tumor samples are engrafted into immunocompromised mice have become an attractive alternative as they can be transplanted through multiple generations,and more efficiently reflect tumor heterogeneity than xenografts derived from human cancer cell lines...
November 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27929457/advanced-animal-model-of-colorectal-metastasis-in-liver-imaging-techniques-and-properties-of-metastatic-clones
#14
Go Oshima, Melinda E Stack, Sean C Wightman, Darren Bryan, Elizabeth Poli, Lai Xue, Kinga B Skowron, Abhineet Uppal, Sean P Pitroda, Xiaona Huang, Mitchell C Posner, Samuel Hellman, Ralph R Weichselbaum, Nikolai N Khodarev
Patients with a limited number of hepatic metastases and slow rates of progression can be successfully treated with local treatment approaches(1,2). However, little is known about the heterogeneity of liver metastases, and animal models capable of evaluating the development of individual metastatic colonies are needed. Here, we present an advanced model of hepatic metastases that provides the ability to quantitatively visualize the development of individual tumor clones in the liver and estimate their growth kinetics and colonization efficiency...
November 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27928788/-basic-and-translational-research-progress-of-gastrointestinal-neuroendocrine-neoplasmas
#15
Yuli Song, Xiaoyi Li, Tiantian Song, Guole Lin, Yuanjia Chen
Gastrointestinal neuroendocrine tumors are a group of highly heterogeneous tumors. Their incidences have increased in the Western countries as well as in Asia for years. In recent years, predominant progression has been made in the basic and translational studies on gastrointestinal neuroendocrine tumors. Gastric neuroendocrine neoplasmas are classified as four types: type I( occurs on the basis of autoimmune atrophic gastritis, type II( clinically manifests as multiple endocrine tumor type I( and Zollinger-Ellison syndrome, type III( is sporadic neuroendocrine neoplasmas, and type IIII( is neuroendocrine carcinoma...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27928786/-implementation-of-multidisciplinary-team-in-the-diagnosis-and-treatment-of-gastroenteropancreatic-neuroendocrine-neoplasm
#16
Panpan Zhang, Lin Shen
Multidisciplinary team(MDT) has been considered as the best practice in the treatment planning and care for patients with cancer around the world. With the increased range and number of specialists involved, multidisciplinary coordination and communication have been enhanced, and the efficiency and quality of diagnosis and treatment of cancer have been improved. Neuroendocrine neoplasm (NEN) is a heterogeneous group of tumors originating from neuroendocrine cells located throughout the body, most of which is gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN)...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27925648/sonographic-evaluation-of-intrathyroid-metastases
#17
J Matthew Debnam, Michael Kwon, Bruno D Fornage, Savitri Krishnamurthy, Gary L Clayman, Beth S Edeiken-Monroe
OBJECTIVES: Intrathyroid metastases from extrathyroid primary tumors are rare. Clinical findings may be subtle, but detection of intrathyroid metastases has improved with sonography. The objective of this study was to evaluate the sonographic appearance of intrathyroid metastases. METHODS: Patients with thyroid masses with cytopathologic features matching those of an extrathyroid primary tumor were retrospectively identified. The appearances of intrathyroid metastases on sonography were reviewed for the following features: size, margin regularity, echogenicity, echotexture, vascularity on power or color Doppler ultrasonography, and the presence or absence of any associated cervical adenopathy...
December 7, 2016: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/27925473/the-role-of-cancer-stem-cells-in-tumor-heterogeneity-and-resistance-to-therapy
#18
Christina Valbirk Konrad, Reshma Murali, Binitha Anu Varghese, Radhika Nair
Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients...
September 3, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27925039/metaplastic-squamous-cell-carcinoma-of-the-breast-a-case-report-and-literature-review
#19
Luciana Graziano, Paschoal Graziano, Almir Galvão Vieira Bitencourt, Daniel Bernal Soto, Alexandre Hiro, Cíntia Camillo Nunes
Metaplastic tumors are rare and represent a heterogeneous group of neoplasms showing dominant areas of non-glandular differentiation. Etiology and pathogenesis of this type of lesion in the breast is uncertain. The most common sources of metastatic squamous cell carcinoma of the breast are lung, esophagus, cervix, and urinary bladder. Squamous cell carcinomas may present clinically with inflammation and average size greater than breast adenocarcinoma. As for imaging studies, mammography shows no typical findings and ultrasound can show a complicated cyst or an inflammatory process, among the differential diagnoses...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27924826/iron-chelators-target-both-proliferating-and-quiescent-cancer-cells
#20
Mårten Fryknäs, Xiaonan Zhang, Ulf Bremberg, Wojciech Senkowski, Maria Hägg Olofsson, Peter Brandt, Ingmar Persson, Padraig D'Arcy, Joachim Gullbo, Peter Nygren, Leoni Kunz Schughart, Stig Linder, Rolf Larsson
Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation...
December 7, 2016: Scientific Reports
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