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https://www.readbyqxmd.com/read/28734796/clonal-composition-of-human-ovarian-cancer-based-on-copy-number-analysis-reveals-a-reciprocal-relation-with-oncogenic-mutation-status
#1
Kazuko Sakai, Masayo Ukita, Jeanette Schmidt, Longyang Wu, Marco De Velasco, Alan Roter, Luis Jevons, Kazuto Nishio, Masaki Mandai
Intratumoral heterogeneity of cancer cells remains largely unexplored. Here we investigated the composition of ovarian cancer and its biological relevance. A whole-genome single nucleotide polymorphism array was applied to detect the clonal composition of 24 formalin-fixed, paraffin-embedded samples of human ovarian cancer. Genome-wide segmentation data consisting of the log2 ratio (log2R) and B allele frequency (BAF) were used to calculate an estimate of the clonal composition number (CC number) for each tumor...
July 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28733443/direct-metabolic-interrogation-of-dihydrotestosterone-biosynthesis-from-adrenal-precursors-in-primary-prostatectomy-tissues
#2
Charles Dai, Yoon-Mi Chung, Evan Kovac, Ziqi Zhu, Jianneng Li, Cristina Magi-Galluzzi, Andrew J Stephenson, Eric A Klein, Nima Sharifi
Purpose: A major mechanism of castration-resistant prostate cancer (CRPC) involves intratumoral biosynthesis of dihydrotestosterone (DHT) from adrenal precursors. We have previously shown that adrenal-derived androstenedione (AD) is the preferred substrate over testosterone (T) for 5α-reductase expressed in metastatic CRPC, bypassing T as an obligate precursor to DHT. However, the metabolic pathway of adrenal-derived DHT biosynthesis has not been rigorously investigated in the setting of primary disease in the prostate...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28733428/tcr-repertoire-intratumor-heterogeneity-in-localized-lung-adenocarcinomas-an-association-with-predicted-neoantigen-heterogeneity-and-postsurgical-recurrence
#3
Alexandre Reuben, Rachel M Gittelman, Jianjun Gao, Jiexin Zhang, Erik Yusko, Chang-Jiun Wu, Ryan Emerson, Jianhua Zhang, Christopher M Tipton, Jun Li, Kelly Quek, Vancheswaran Gopalakrishnan, Runzhe Chen, Luis Vence, Tina Cascone, Marissa Vignali, Junya Fujimoto, Jaime Rodriguez-Canales, Edwin R Parra, Latasha D Little, Curtis Gumbs, Marie-Andrée Forget, Lorenzo Federico, Cara Haymaker, Carmen Behrens, Sharon Benzeno, Chantale Bernatchez, Boris Sepesi, Don L Gibbons, Jennifer A Wargo, William N William, Stephen G Swisher, John Heymach, Harlan Robins, J Jack Lee, Padmanee Sharma, James P Allison, P Andrew Futreal, Ignacio I Wistuba, Jianjun Zhang
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens were shown to alter tumor immunogenicity through T cell responses. Here, we performed sequencing of the T cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T cell density and clonality with the majority of T cell clones restricted to individual tumor regions...
July 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28729677/engineering-tumour-cell-binding-synthetic-polymers-with-sensing-dense-transporters-associated-with-aberrant-glutamine-metabolism
#4
Naoki Yamada, Yuto Honda, Hiroyasu Takemoto, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Masamitsu Konno, Hideshi Ishii, Masaki Mori, Nobuhiro Nishiyama
Increased glutamine uptake toward the elevated glutaminolysis is one of the hallmarks of tumour cells. This aberrant glutamine metabolism has recently attracted considerable attention as a diagnostic and therapeutic target. Herein, we developed glutamine-functionalized polymer to achieve a selective high affinity to tumour cells overexpressing glutaminolysis-related transporter ASCT2. In in vitro study, our developed polymer exhibited faster and higher cellular uptake in tumour cells than that in normal cells...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28727185/automation-of-pattern-recognition-analysis-of-dynamic-contrast-enhanced-mri-data-to-characterize-intratumoral-vascular-heterogeneity
#5
SoHyun Han, Radka Stoyanova, Hansol Lee, Sean D Carlin, Jason A Koutcher, HyungJoon Cho, Ellen Ackerstaff
PURPOSE: To automate dynamic contrast-enhanced MRI (DCE-MRI) data analysis by unsupervised pattern recognition (PR) to enable spatial mapping of intratumoral vascular heterogeneity. METHODS: Three steps were automated. First, the arrival time of the contrast agent at the tumor was determined, including a calculation of the precontrast signal. Second, four criteria-based algorithms for the slice-specific selection of number of patterns (NP) were validated using 109 tumor slices from subcutaneous flank tumors of five different tumor models...
July 20, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28726304/retardation-of-antigen-release-from-dna-hydrogel-using-cholesterol-modified-dna-for-increased-antigen-specific-immune-response
#6
Yuka Umeki, Masaaki Saito, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
Our previous study indicates that cationization of an antigen is effective for sustained release of both immunostimulatory DNA containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides, or CpG DNA, and antigen from a DNA hydrogel. Another approach to sustained antigen release would increase the applicability and versatility of the system. In this study, a hydrophobic interaction-based sustained release system of ovalbumin (OVA), a model antigen, from immunostimulatory CpG DNA hydrogel is developed by the use of cholesterol-modified DNA and urea-denatured OVA (udOVA)...
July 20, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28726259/characterization-of-adenoviral-transduction-profile-in-prostate-cancer-cells-and-normal-prostate-tissue
#7
Jianzhong Ai, Phillip W L Tai, Yi Lu, Jia Li, Hong Ma, Qin Su, Qiang Wei, Hong Li, Guangping Gao
BACKGROUND: Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases...
July 20, 2017: Prostate
https://www.readbyqxmd.com/read/28724615/glioblastoma-cellular-cross-talk-converges-on-nf-%C3%AE%C2%BAb-to-attenuate-egfr-inhibitor-sensitivity
#8
Ciro Zanca, Genaro R Villa, Jorge A Benitez, Amy Haseley Thorne, Tomoyuki Koga, Matteo D'Antonio, Shiro Ikegami, Jianhui Ma, Antonia D Boyer, Afsheen Banisadr, Nathan M Jameson, Alison D Parisian, Olesja V Eliseeva, Gabriela F Barnabe, Feng Liu, Sihan Wu, Huijun Yang, Jill Wykosky, Kelly A Frazer, Vladislav V Verkhusha, Maria G Isaguliants, William A Weiss, Timothy C Gahman, Andrew K Shiau, Clark C Chen, Paul S Mischel, Webster K Cavenee, Frank B Furnari
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs)...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28723673/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#9
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#10
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722675/using-droplet-digital-pcr-to-analyze-mycn-and-alk-copy-number-in-plasma-from-patients-with-neuroblastoma
#11
Marco Lodrini, Annika Sprüssel, Kathy Astrahantseff, Daniela Tiburtius, Robert Konschak, Holger N Lode, Matthias Fischer, Ulrich Keilholz, Angelika Eggert, Hedwig E Deubzer
The invasive nature of surgical biopsies deters sequential application, and single biopsies often fail to reflect tumor dynamics, intratumor heterogeneity and drug sensitivities likely to change during tumor evolution and treatment. Implementing molecular characterization of cell-free neuroblastoma-derived DNA isolated from blood plasma could improve disease assessment for treatment selection and monitoring of patients with high-risk neuroblastoma. We established droplet digital PCR (ddPCR) protocols for MYCN and ALK copy number status in plasma from neuroblastoma patients...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722661/dck-expression-a-potential-predictive-biomarker-in-the-adjuvant-gemcitabine-chemotherapy-for-biliary-tract-cancer-after-surgical-resection-results-from-a-phase-ii-study
#12
Sang Myung Woo, Kyong-Ah Yoon, Eun Kyung Hong, Weon Seo Park, Sung-Sik Han, Sang-Jae Park, Jungnam Joo, Eun Young Park, Ju Hee Lee, Yun-Hee Kim, Tae Hyun Kim, Woo Jin Lee
The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721452/enhanced-efficacy-of-radiofrequency-ablation-for-hepatocellular-carcinoma-using-a-novel-vascular-disrupting-agent-ckd-516
#13
Su Jung Ham, YoonSeok Choi, Seul-I Lee, Jinil Kim, Young Il Kim, Jin Wook Chung, Kyung Won Kim
BACKGROUND: CKD-516 is a novel vascular disrupting agent that shuts down intratumoral blood flow. We therefore hypothesized that concomitant administration of CKD-516 would enhance the therapeutic efficacy of radiofrequency ablation (RFA) by reducing heat sink effects. We assessed the effects of the combination of CKD-516 and RFA in a rat orthotopic hepatocellular carcinoma (HCC) model. METHODS: Rat HCC cells (N1-S1) were engrafted into the hepatic lobe of Sprague-Dawley (SD) rats...
July 18, 2017: Hepatology International
https://www.readbyqxmd.com/read/28719907/tumor-heterogeneity-in-lymphomas-a-different-breed
#14
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28718726/effects-of-the-notch1-signaling-pathway-on-human-lung-cancer-a549-cells
#15
Yun Zeng, Bijian Yin, Xinwei Wang, Guohao Xia, Zhengjie Shen, Wenzhe Gu, Mianhua Wu
PURPOSE: To evaluate the effects of the Notch1 signaling pathway on human lung cancer A549 cells. MATERIALS AND METHODS: A549 cells were transfected with recombinant plasmids. Cell proliferation was detected by MTT assay. A tumor-bearing mouse model was established for intratumoral gene injection. Apoptosis-related factors were detected by immunohistochemical assay. Caspase-8, caspase-3, caspase-9, PI3K, pAkt and pSTAT3 expressions were detected by Western blotting...
July 18, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28718406/targeting-hypoxia-inducible-factors-for-antiangiogenic-cancer-therapy
#16
REVIEW
Sergio Rey, Luana Schito, Bradly G Wouters, Scott Eliasof, Robert S Kerbel
Hypoxia (low O2) is a pathobiological hallmark of solid cancers, resulting from the imbalance between cellular O2 consumption and availability. Hypoxic cancer cells (CCs) stimulate blood vessel sprouting (angiogenesis), aimed at restoring O2 delivery to the expanding tumor masses through the activation of a transcriptional program mediated by hypoxia-inducible factors (HIFs). Here, we review recent data suggesting that the efficacy of antiangiogenic (AA) therapies is limited in some circumstances by HIF-dependent compensatory responses to increased intratumoral hypoxia...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716985/two-microrna-signatures-for-malignancy-and-immune-infiltration-predict-overall-survival-in-advanced-epithelial-ovarian-cancer
#17
Ilya Korsunsky, Janaki Parameswaran, Iuliana Shapira, John Lovecchio, Andrew Menzin, Jill Whyte, Lisa Dos Santos, Sharon Liang, Tawfiqul Bhuiya, Mary Keogh, Houman Khalili, Cassandra Pond, Anthony Liew, Andrew Shih, Peter K Gregersen, Annette T Lee
MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions...
July 17, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28716121/identification-of-trunk-mutations-in-gastric-carcinoma-a-case-study
#18
Zhan Zhou, Shanshan Wu, Jun Lai, Yuan Shi, Chixiao Qiu, Zhe Chen, Yufeng Wang, Xun Gu, Jie Zhou, Shuqing Chen
BACKGROUND: Intratumor heterogeneity (ITH) poses an urgent challenge for cancer precision medicine because it can cause drug resistance against cancer target therapy and immunotherapy. The search for trunk mutations that are present in all cancer cells is therefore critical for each patient. CASE PRESENTATION: In this study, we aimed to evaluate the efficiency of multiregional sequencing for the identification of trunk mutations present in all regions of a tumor as a case study...
July 17, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28714990/an-approach-to-suppress-the-evolution-of-resistance-in-braf-v600e-mutant-cancer
#19
Yaohua Xue, Luciano Martelotto, Timour Baslan, Alberto Vides, Martha Solomon, Trang Thi Mai, Neelam Chaudhary, Greg J Riely, Bob T Li, Kerry Scott, Fabiola Cechhi, Ulrika Stierner, Kalyani Chadalavada, Elisa de Stanchina, Sarit Schwartz, Todd Hembrough, Gouri Nanjangud, Michael F Berger, Jonas Nilsson, Scott W Lowe, Jorge S Reis-Filho, Neal Rosen, Piro Lito
The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAF(amp)) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or in combination with other ERK signaling inhibitors. Single-cell sequencing and multiplex fluorescence in situ hybridization analyses mapped the emergence of extra-chromosomal amplification in parallel evolutionary trajectories that arose in the same tumor shortly after treatment...
July 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28714406/role-of-the-immune-component-of-tumor-microenvironment-in-the-efficiency-of-cancer-treatment-perspectives-for-the-personalized-therapy
#20
Marina Stakheyeva, Vladimir Riabov, Irina Mitrofanova, Nikolai Litviakov, Evgeny Choynzonov, Nadezhda Cherdyntseva, Julia Kzhyshkowska
Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones...
July 14, 2017: Current Pharmaceutical Design
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