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intratumor heterogeneity

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https://www.readbyqxmd.com/read/29779072/intratumoral-heterogeneity-on-dedicated-breast-positron-emission-tomography-predicts-malignancy-grade-of-breast-cancer
#1
Norio Masumoto, Takayuki Kadoya, Shinsuke Sasada, Akiko Emi, Koji Arihiro, Morihito Okada
PURPOSE: Dedicated breast positron emission tomography (DbPET) provides detailed high-resolution images and can detect intratumoral heterogeneity using 18 F-fluorodeoxyglucose (FDG). We aimed to evaluate the correlation between FDG uptake on DbPET and the clinicopathological features of breast cancer, particularly those with an intratumoral heterogeneous distribution of FDG on DbPET. METHODS: We evaluated 195 consecutive patients with invasive breast cancer who underwent preoperative whole-body PET (WBPET) and DbPET concurrently between January 2016 and March 2017...
May 19, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#2
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774112/rare-genetic-heterogeneity-within-single-tumor-discovered-for-the-first-time-in-colorectal-liver-metastases-after-liver-resection
#3
Mylène Sebagh, Nelly Bosselut, Alexandre Dos Santos, Marc-Antoine Allard, Aldrick Ruiz, Raphaël Saffroy, Daniel Cherqui, Eric Vibert, Denis Castaing, René Adam, Antonio Sa Cunha, Antoinette Lemoine
Effective individualized treatment of patients with colorectal liver metastases (CLM) requires tumor genotyping, usually based on the analysis of one single sample per patient. Therapy failure may partially be explained by sampling errors and/or intratumoral genetic heterogeneity. We aimed to demonstrate intratumoral genetic heterogeneity in CLM and enable pathologists to select tumor tissue for genotyping. All the tumors of 86 patients who underwent liver resection for a single CLM were reviewed. Of the 86 patients, 66 patients received chemotherapy and 20 patients did not receive chemotherapy before liver resection...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771717/prognostic-predictive-value-of-preoperative-intratumoral-2-deoxy-2-18f-fluoro-d-glucose-uptake-heterogeneity-in-patients-with-high-grade-serous-ovarian-cancer
#4
Shuai Liu, Zheng Feng, Zhaoxia Jiang, Hao Wen, Junyan Xu, Herong Pan, Yu Deng, Lei Zhang, Xingzhu Ju, Xiaojun Chen, Xiaohua Wu
OBJECTIVE: This study aimed to explore the clinical and prognostic significance of pretreatment positron-emission tomography/computed tomography (PET/CT) parameters, especially 2-deoxy-2-(F)fluoro-D-glucose-based heterogeneity, in high-grade serous ovarian cancer (HGSC). MATERIALS AND METHODS: We retrospectively investigated 56 patients with HGSC who underwent PET/CT before primary surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy...
May 16, 2018: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/29764517/new-insights-from-the-widening-homogeneity-perspective-to-target-intratumor-heterogeneity
#5
REVIEW
Mengying Tong, Ziqian Deng, Xiaolong Zhang, Bin He, Mengying Yang, Wei Cheng, Quentin Liu
Precision medicine has shed new light on the treatment of heterogeneous cancer patients. However, intratumor heterogeneity strongly constrains the clinical benefit of precision medicine. Thus, rethinking therapeutic strategies from a different facet within the precision medicine framework will not only diversify clinical interventions, but also provide an avenue for precision medicine. Here, we explore the current approaches for targeting intratumor heterogeneity and their limitations. Furthermore, we propose a theoretical strategy with a "homogenization" feature based on iatrogenic evolutionary selection to target intratumor heterogeneity...
May 4, 2018: Cancer communications
https://www.readbyqxmd.com/read/29761158/phase-ii-study-of-ruxolitinib-a-selective-jak1-2-inhibitor-in-patients-with-metastatic-triple-negative-breast-cancer
#6
Daniel G Stover, Carlos R Gil Del Alcazar, Jane Brock, Hao Guo, Beth Overmoyer, Justin Balko, Qiong Xu, Aditya Bardia, Sara M Tolaney, Rebecca Gelman, Maxwell Lloyd, Yu Wang, Yaomin Xu, Franziska Michor, Vivian Wang, Eric P Winer, Kornelia Polyak, Nancy U Lin
Preclinical data support a role for the IL-6/JAK2/STAT3 signaling pathway in breast cancer. Ruxolitinib is an orally bioavailable receptor tyrosine inhibitor targeting JAK1 and JAK2. We evaluated the safety and efficacy of ruxolitinib in patients with metastatic breast cancer. This was a non-randomized phase II study enrolling patients with refractory, metastatic triple-negative breast cancer. The primary endpoint was objective response by RECIST 1.1. The study was designed to enroll patients whose archival tumor tissue was pSTAT3-positive ( T -score >5) by central immunohistochemistry...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29737395/estimating-intratumoral-heterogeneity-from-spatiotemporal-data
#7
E M Rutter, H T Banks, K B Flores
Glioblastoma multiforme (GBM) is a malignant brain cancer with a tendency to both migrate and proliferate. We propose modeling GBM with heterogeneity in cell phenotypes using a random differential equation version of the reaction-diffusion equation, where the parameters describing diffusion (D) and proliferation ([Formula: see text]) are random variables. We investigate the ability to perform the inverse problem to recover the probability distributions of D and [Formula: see text] using the Prohorov metric, for a variety of probability distribution functions...
May 8, 2018: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/29732370/microenvironmental-signals-and-biochemical-information-processing-cooperative-determinants-of-intratumoral-plasticity-and-heterogeneity
#8
REVIEW
Alexander E Davies, John G Albeck
Intra-tumor cellular heterogeneity is a major challenge in cancer therapy. Tumors are composed of multiple phenotypic subpopulations that vary in their ability to initiate metastatic tumors and in their sensitivity to chemotherapy. In many cases, cells can transition between these subpopulations, not by genetic mutation, but instead through reversible changes in signal transduction or gene expression programs. This plasticity begins at the level of the microenvironment where local autocrine and paracrine signals, exosomes, tumor-stroma interactions, and extracellular matrix (ECM) composition create a signaling landscape that varies over space and time...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29721371/complimentary-mechanisms-of-dual-checkpoint-blockade-expand-unique-t-cell-repertoires-and-activate-adaptive-anti-tumor-immunity-in-triple-negative-breast-tumors
#9
Erika J Crosby, Junping Wei, Xiao Yi Yang, Gangjun Lei, Tao Wang, Cong-Xiao Liu, Pankaj Agarwal, Alan J Korman, Michael A Morse, Kenneth Gouin, Simon R V Knott, H Kim Lyerly, Zachary C Hartman
Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29720487/metabolic-heterogeneity-on-baseline-18fdg-pet-ct-scan-is-a-predictor-of-outcome-in-primary-mediastinal-b-cell-lymphoma
#10
Luca Ceriani, Lisa Milan, Maurizio Martelli, Andrés J M Ferreri, Luciano Cascione, Pier Luigi Zinzani, Alice Di Rocco, Annarita Conconi, Anastasios Stathis, Franco Cavalli, Monica Bellei, Kelly Cozens, Elena Porro, Luca Giovanella, Peter W Johnson, Emanuele Zucca
An important unmet need in the management of primary mediastinal B-cell lymphoma (PMBCL) is to identify the patients for whom first line therapy will fail, in order to intervene before the lymphoma becomes refractory. High heterogeneity of intratumoral 18F-fluorodeoxyglucose (18FDG) uptake distribution on positron emission tomography/computed tomography (PET/CT) scans has been suggested as a possible marker of chemo-resistance in solid tumors. In the present study, we investigated the prognostic value of metabolic heterogeneity (MH) in 103 PMBCL patients prospectively enrolled in the International Extranodal Lymphoma Study Group (IELSG) 26 study, aimed at clarifying the role of PET in this lymphoma subtype...
May 2, 2018: Blood
https://www.readbyqxmd.com/read/29718986/self-digitization-chip-for-single-cell-genotyping-of-cancer-related-mutations
#11
Alison M Thompson, Jordan L Smith, Luke D Monroe, Jason E Kreutz, Thomas Schneider, Bryant S Fujimoto, Daniel T Chiu, Jerald P Radich, Amy L Paguirigan
Cancer is a heterogeneous disease, and patient-level genetic assessments can guide therapy choice and impact prognosis. However, little is known about the impact of genetic variability within a tumor, intratumoral heterogeneity (ITH), on disease progression or outcome. Current approaches using bulk tumor specimens can suggest the presence of ITH, but only single-cell genetic methods have the resolution to describe the underlying clonal structures themselves. Current techniques tend to be labor and resource intensive and challenging to characterize with respect to sources of biological and technical variability...
2018: PloS One
https://www.readbyqxmd.com/read/29718366/intratumoral-heterogeneity-of-oxygen-metabolism-and-neovascularization-uncovers-two-survival-relevant-subgroups-of-idh1-wild-type-glioblastoma
#12
Andreas Stadlbauer, Max Zimmermann, Arnd Doerfler, Stefan Oberndorfer, Michael Buchfelder, Roland Coras, Melitta Kitzwögerer, Karl Roessler
Background: The intratumoral heterogeneity of oxygen metabolism in combination with variable patterns of neovascularization (NV) as well as reprogramming of energy metabolism affects the landscape of tumor microenvironments (TMEs) in glioblastoma. Knowledge of the hypoxic and perivascular niches within the TME is essential for understanding treatment failure. Methods: Fifty-two patients with untreated glioblastoma (IDH1 wildtype) were examined with a physiological MRI protocol including a multiparametric quantitative blood-oxygen-level-dependent (qBOLD) approach and vascular architecture mapping (VAM)...
April 28, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29714680/intratumoral-spatial-heterogeneity-at-perfusion-mr-imaging-predicts-recurrence-free-survival-in-locally-advanced-breast-cancer-treated-with-neoadjuvant-chemotherapy
#13
Jia Wu, Guohong Cao, Xiaoli Sun, Juheon Lee, Daniel L Rubin, Sandy Napel, Allison W Kurian, Bruce L Daniel, Ruijiang Li
Purpose To characterize intratumoral spatial heterogeneity at perfusion magnetic resonance (MR) imaging and investigate intratumoral heterogeneity as a predictor of recurrence-free survival (RFS) in breast cancer. Materials and Methods In this retrospective study, a discovery cohort (n = 60) and a multicenter validation cohort (n = 186) were analyzed. Each tumor was divided into multiple spatially segregated, phenotypically consistent subregions on the basis of perfusion MR imaging parameters. The authors first defined a multiregional spatial interaction (MSI) matrix and then, based on this matrix, calculated 22 image features...
April 27, 2018: Radiology
https://www.readbyqxmd.com/read/29709260/noninvasive-pet-imaging-of-t-cells
#14
REVIEW
Weijun Wei, Dawei Jiang, Emily B Ehlerding, Quanyong Luo, Weibo Cai
The rapidly evolving field of cancer immunotherapy recently saw the approval of several new therapeutic antibodies. Several cell therapies, for example, chimeric antigen receptor-expressing T cells (CAR-T), are currently in clinical trials for a variety of cancers and other diseases. However, approaches to monitor changes in the immune status of tumors or to predict therapeutic responses are limited. Monitoring lymphocytes from whole blood or biopsies does not provide dynamic and spatial information about T cells in heterogeneous tumors...
May 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29708949/the-genomics-of-renal-cell-carcinoma-and-its-role-in-renal-mass-biopsy
#15
Simpa S Salami, Arvin K George, Aaron M Udager
PURPOSE OF REVIEW: Large-scale genomic profiling has shed new light on the molecular underpinnings of renal cell carcinoma (RCC), spurring a much needed refinement of RCC subclassification based on an integrative assessment of histopathologic features and molecular alterations. At the same time, renal mass biopsies have become increasingly commonplace, necessitating ancillary tools to help guide clinical management. Herein, we briefly review our current understanding of RCC genomics, highlighting areas of possible clinical utility, as well as potential limitations, for renal mass biopsies...
April 27, 2018: Current Opinion in Urology
https://www.readbyqxmd.com/read/29708354/-new-approaches-for-chemosensitivity-testing-in-malignant-diseases
#16
Lucia Sommerová, Eva Michalová, Roman Hrstka
BACKGROUND: Due to the irreplaceable role of chemotherapy in cancer treatment, research has focused on improving the efficacies of individual drugs and minimizing, or completely suppressing, their negative side effects. Based on long-term experience and the results of clinical trials, the selection of appropriate treatment is currently based on classical clinical diagnostic criteria, such as tumor size, grade, and the presence or absence of standard markers. However, complications arise due to variability between patients and tumor heterogeneity...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29707277/intratumoral-heterogeneity-of-notch1-expression-in-small-cell-lung-cancer
#17
EDITORIAL
Takaaki Ito
No abstract text is available yet for this article.
March 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29707265/a-richer-understanding-of-intratumoral-heterogeneity-single-cell-genomics-put-it-within-reach
#18
EDITORIAL
Xuetao Li, Jun Hou
No abstract text is available yet for this article.
March 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29702286/expression-patterns-prognostic-value-and-intratumoral-heterogeneity-of-pd-l1-and-pd-1-in-thymoma-and-thymic-carcinoma
#19
Dwight Owen, Benjamin Chu, Amy M Lehman, Lakshmanan Annamalai, Jennifer H Yearley, Konstantin Shilo, Gregory A Otterson
INTRODUCTION: Thymic epithelial tumors (TET) including thymoma and thymic carcinoma are rare tumors with little data available to guide treatment. Immunotherapy with checkpoint blockade has shown promising activity, but data regarding the expression patterns and prognostic implications of programmed death 1 (PD-1) and its ligand (PD-L1) in TET have yielded conflicting results. Intratumoral heterogeneity of PD-1/L1 expression has been demonstrated in other cancers but has not been described in the TET literature...
April 24, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29700472/inferring-parsimonious-migration-histories-for-metastatic-cancers
#20
Mohammed El-Kebir, Gryte Satas, Benjamin J Raphael
Metastasis is the migration of cancerous cells from a primary tumor to other anatomical sites. Although metastasis was long thought to result from monoclonal seeding, or single cellular migrations, recent phylogenetic analyses of metastatic cancers have reported complex patterns of cellular migrations between sites, including polyclonal migrations and reseeding. However, accurate determination of migration patterns from somatic mutation data is complicated by intratumor heterogeneity and discordance between clonal lineage and cellular migration...
April 26, 2018: Nature Genetics
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