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intratumor heterogeneity

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https://www.readbyqxmd.com/read/28221191/the-assessment-of-estrogen-receptor-status-and-its-intratumoral-heterogeneity-in-breast-cancer-patients-by-using-18-f-fluoroestradiol-pet-ct
#1
Zhongyi Yang, Yifei Sun, Xiaoping Xu, Yongping Zhang, Jianping Zhang, Jing Xue, Mingwei Wang, Huiyu Yuan, Silong Hu, Wei Shi, Beiling Zhu, Yingjian Zhang
AIM: The aim of this study was to investigate the clinical value of F-fluoroestradiol (F-FES) PET/CT in the assessment of the estrogen receptor (ER) and its intratumoral heterogeneity in breast cancer patients. METHODS: Forty-six female patients (50 lesions) with histologically confirmed invasive breast cancer who underwent both F-FES and F-FDG PET/CT in our center were retrospectively included. All the patients enrolled were scheduled to undergo biopsy. The F-FES and FDG uptakes were compared with pathological features (tumor size, ER, progesterone receptor, human epidermal growth factor receptor 2, and Ki67%)...
February 17, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28202525/oncogenic-effects-of-high-mapk-activity-in-colorectal-cancer-mark-progenitor-cells-and-persist-irrespective-of-ras-mutations
#2
Cristina Blaj, Eva Marina Schmidt, Sebastian Lamprecht, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
About 40% of colorectal cancers have mutations in KRAS accompanied by downstream activation of MAPK signaling which promotes tumor invasion and progression. Here we report that MAPK signaling shows strong intratumoral heterogeneity and unexpectedly remains regulated in colorectal cancer irrespective of KRAS mutation status. Using primary colorectal cancer tissues, xenograft models and MAPK reporter constructs, we showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition (EMT), and expressed markers related to colon cancer stem cells...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197369/the-transcriptome-of-lung-tumor-infiltrating-dendritic-cells-reveals-a-tumor-supporting-phenotype-and-a-microrna-signature-with-negative-impact-on-clinical-outcome
#3
Lotte Pyfferoen, Elisabeth Brabants, Celine Everaert, Nancy De Cabooter, Kelly Heyns, Kim Deswarte, Manon Vanheerswynghels, Sofie De Prijck, Glenn Waegemans, Melissa Dullaers, Hamida Hammad, Olivier De Wever, Pieter Mestdagh, Jo Vandesompele, Bart N Lambrecht, Karim Y Vermaelen
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs are emerging as clinically relevant parameters in lung cancer. In this study, we used an orthotopic preclinical model of lung cancer to dissect how the lung tumor micro-environment affects tissue-resident DCs and extract novel biologically and clinically relevant information...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195905/value-of-intratumoral-metabolic-heterogeneity-and-quantitative-18f-fdg-pet-ct-parameters-to-predict-prognosis-in-patients-with-hpv-positive-primary-oropharyngeal-squamous-cell-carcinoma
#4
Esther Mena, Mehdi Taghipour, Sara Sheikhbahaei, Abhinav K Jha, Arman Rahmim, Lilja Solnes, Rathan M Subramaniam
OBJECTIVE: The aim of this study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative FDG PET/CT imaging parameters for predicting patient outcomes in primary oropharyngeal squamous cell cancer (OPSCC). PATIENTS AND METHODS: We retrospectively investigated 105 patients with HPV-positive OPSCC. SUVmax and metabolic tumor volume (MTV) were measured for the primary tumors and when available for the metastatic sites. Primary tumor intratumoral metabolic heterogeneity was calculated as the area under a cumulative SUV volume histograms curve (AUC-CSH)...
February 13, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28195880/pd-l1-expression-and-intratumoral-heterogeneity-across-breast-cancer-subtypes-and-stages-an-assessment-of-245-primary-and-40-metastatic-tumors
#5
Erik A Dill, Alejandro A Gru, Kristen A Atkins, Lisa A Friedman, Margaret E Moore, Timothy N Bullock, Janet V Cross, Patrick M Dillon, Anne M Mills
Tumor expression of programmed cell death ligand 1 (PD-L1) is associated with immune evasion in a variety of malignancies, including a subset of triple-negative breast carcinomas, and may mark cancers as susceptible to PD-1/PD-L1 inhibitor therapies. We herein characterize PD-L1 expression in breast cancers across the full range of histomorphologies and investigate its intratumoral heterogeneity and fidelity across primaries and metastases. A total of 245 primary and 40 metastatic (20 nodal, 20 distant) breast carcinomas were evaluated with PD-L1 immunohistochemistry on tissue microarray...
March 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28187284/clonal-heterogeneity-and-tumor-evolution-past-present-and-the-future
#6
REVIEW
Nicholas McGranahan, Charles Swanton
Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187033/prognostic-significance-of-stromal-versus-intratumoral-infiltrating-lymphocytes-in-different-subtypes-of-breast-cancer-treated-with-cytotoxic-neoadjuvant-chemotherapy
#7
Thaer Khoury, Vidya Nagrale, Mateusz Opyrchal, Xuan Peng, Dan Wang, Song Yao
BACKGROUND: The aim of the study was to investigate if there were differences in associations of stromal versus intratumoral tumor infiltrating lymphocytes (TILs) with pathology complete response (pCR) among breast cancer (BC) subtypes treated with neoadjuvant therapy. MATERIALS AND METHODS: The hematoxylin and eosin slides of BC-core biopsy consecutive cases (n=331) were reviewed from a single institution between 2000 and 2014. TIL-stroma (TIL-str) was scored from 0% to 100%...
February 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28185165/oncolytic-viruses-emerging-options-for-the-treatment-of-breast-cancer
#8
REVIEW
Yogesh R Suryawanshi, Tiantian Zhang, Karim Essani
Breast cancer (BC) is the most common type of cancer among women and is the second most common cause of cancer-related deaths, following lung cancer. Severe toxicity associated with a long-term use of BC chemo- and radiotherapy makes it essential to look for newer therapeutics. Additionally, molecular heterogeneity at both intratumoral and intertumoral levels among BC subtypes is known to result in a differential response to standard therapeutics. Oncolytic viruses (OVs) have emerged as one of the most promising treatment options for BC...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28184407/epstein-barr-virus-associated-gastric-cancer-reveals-intratumoral-heterogeneity-of-pik3ca-mutations
#9
C Böger, S Krüger, H M Behrens, S Bock, J Haag, H Kalthoff, C Röcken
No abstract text is available yet for this article.
February 9, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28176411/diffusion-radiomics-analysis-of-intratumoral-heterogeneity-in-a-murine-prostate-cancer-model-following-radiotherapy-pixelwise-correlation-with-histology
#10
Yu-Chun Lin, Gigin Lin, Ji-Hong Hong, Yi-Ping Lin, Fang-Hsin Chen, Shu-Hang Ng, Chun-Chieh Wang
PURPOSE: To investigate the biological meaning of apparent diffusion coefficient (ADC) values in tumors following radiotherapy. MATERIALS AND METHODS: Five mice bearing TRAMP-C1 tumor were half-irradiated with a dose of 15 Gy. Diffusion-weighted images, using multiple b-values from 0 to 3000 s/mm(2) , were acquired at 7T on day 6. ADC values calculated by a two-point estimate and monoexponential fitting of signal decay were compared between the irradiated and nonirradiated regions of the tumor...
February 8, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28167243/prediction-of-recurrence-by-preoperative-intratumoral-fdg-uptake-heterogeneity-in-endometrioid-endometrial-cancer
#11
Seo Young Kang, Gi Jeong Cheon, Maria Lee, Hee Seung Kim, Jae-Weon Kim, Noh-Hyun Park, Yong Sang Song, Hyun Hoon Chung
PURPOSE: To investigate the prognostic value of preoperative intratumoral (18)F-FDG uptake heterogeneity (IFH) derived from positron emission tomography (PET)/computed tomography (CT) in patients with endometrioid endometrial cancer. METHODS: We retrospectively evaluated clinicopathological data from patients with pathologically proven endometrioid endometrial cancer who had undergone (18)F-FDG PET/CT scans before surgery. Patients were divided into two groups according to their IFH...
February 3, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28166195/detecting-intratumoral-heterogeneity-of-egfr-activity-by-liposome-based-in-vivo-transfection-of-a-fluorescent-biosensor
#12
G Weitsman, N J Mitchell, R Evans, A Cheung, T L Kalber, R Bofinger, G O Fruhwirth, M Keppler, Z V F Wright, P R Barber, P Gordon, T de Koning, W Wulaningsih, K Sander, B Vojnovic, S Ameer-Beg, M Lythgoe, J N Arnold, E Årstad, F Festy, H C Hailes, A B Tabor, T Ng
Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28165479/whole-genome-single-cell-copy-number-profiling-from-formalin-fixed-paraffin-embedded-samples
#13
Luciano G Martelotto, Timour Baslan, Jude Kendall, Felipe C Geyer, Kathleen A Burke, Lee Spraggon, Salvatore Piscuoglio, Kalyani Chadalavada, Gouri Nanjangud, Charlotte K Y Ng, Pamela Moody, Sean D'Italia, Linda Rodgers, Hilary Cox, Arnaud da Cruz Paula, Asya Stepansky, Michail Schizas, Hannah Y Wen, Tari A King, Larry Norton, Britta Weigelt, James B Hicks, Jorge S Reis-Filho
A substantial proportion of tumors consist of genotypically distinct subpopulations of cancer cells. This intratumor genetic heterogeneity poses a substantial challenge for the implementation of precision medicine. Single-cell genomics constitutes a powerful approach to resolve complex mixtures of cancer cells by tracing cell lineages and discovering cryptic genetic variations that would otherwise be obscured in tumor bulk analyses. Because of the chemical alterations that result from formalin fixation, single-cell genomic approaches have largely remained limited to fresh or rapidly frozen specimens...
February 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28161329/mitochondria-and-cancer-chemoresistance
#14
REVIEW
Flora Guerra, Arnaldo A Arbini, Loredana Moro
Mitochondria, known for more than a century as the energy powerhouse of a cell, represent key intracellular signaling hub that are emerging as important determinants of several aspects of cancer development and progression, including metabolic reprogramming, acquisition of metastatic capability, and response to chemotherapeutic drugs. The majority of cancer cells harbors somatic mutations in the mitochondrial genome (mtDNA) and/or alterations in the mtDNA content, leading to mitochondrial dysfunction. Decreased mtDNA content is also detected in tumor-initiating cells, a subpopulation of cancer cells that are believed to play an integral role in cancer recurrence following chemotherapy...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28154920/high-grade-serous-ovarian-cancer-the-clone-wars
#15
REVIEW
Aleksander Salomon-Perzyński, Magdalena Salomon-Perzyńska, Bogdan Michalski, Violetta Skrzypulec-Plinta
BACKGROUND: The last 5 years' studies using next-generation sequencing provided evidences that many types of solid tumors present spatial and temporal genetic heterogeneity and are composed of multiple populations of genetically distinct subclones that evolve over time following a pattern of branched evolution. The evolutionary nature of cancer has been proposed as the major contributor to drug resistance and treatment failure. In this review, we present the current state of knowledge about the clonal evolution of high-grade serous ovarian cancer and discuss the challenge that clonal evolution poses for efforts to achieve an optimal cancer control...
February 3, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28151756/recent-developments-in-the-management-of-germ-cell-tumors
#16
Pavlos Msaouel, Mehmet A Bilen, Miao Zhang, Matthew Campbell, Jennifer Wang, Shi-Ming Tu
PURPOSE OF REVIEW: In the present review, we summarize the recent developments in the management of germ cell tumors (GCTs). RECENT FINDINGS: Treatment-related acute and late-onset toxicity remains a key challenge in the management of GCTs. Recent data show that patients with large retroperitoneal lymph node metastases are at increased risk of venous thromboembolism and may benefit from prophylactic anticoagulation. Predictive models have been developed to identify patients with residual retroperitoneal lymph node masses who are more likely to benefit from surgical resection...
February 1, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28146430/intratumoral-heterogeneity-of-intrahepatic-cholangiocarcinoma
#17
Dirk Walter, Claudia Döring, Magdalena Feldhahn, Florian Battke, Sylvia Hartmann, Ria Winkelmann, Markus Schneider, Katrin Bankov, Andreas Schnitzbauer, Stefan Zeuzem, Martin Leo Hansmann, Jan Peveling-Oberhag
No personalized therapy regimens could demonstrate a benefit in survival of intrahepatic cholangiocarcinoma (iCCA). Since genetic heterogeneity might influence single biopsy based targeted therapy or the outcome of clinical trials, aim of the present study was to investigate intratumoral heterogeneity of iCCA by whole exome sequencing. Therefore, samples from tumor center and tumor periphery of large iCCA lesions as well as a control from healthy liver tissue were obtained from four patients and whole exome sequencing was performed...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28145097/multiregion-ultra-deep-sequencing-reveals-early-intermixing-and-variable-levels-of-intratumoral-heterogeneity-in-colorectal-cancer
#18
Yuka Suzuki, Sarah Boonhsi Ng, Clarinda Chua, Wei Qiang Leow, Jermain Chng, Shi Yang Liu, Kalpana Ramnarayanan, Anna Gan, Dan Liang Ho, Rachel Ten, Yan Su, Alexandar Lezhava, Jiunn Herng Lai, Dennis Koh, Kiat Hon Lim, Patrick Tan, Steven G Rozen, Iain Beehuat Tan
Intratumor heterogeneity (ITH) contributes to cancer progression and chemoresistance. We sought to comprehensively describe ITH of somatic mutations, copy number, and transcriptomic alterations involving clinically and biologically relevant gene pathways in colorectal cancer (CRC). We performed multiregion, high-depth (384× on average) sequencing of 799 cancer-associated genes in 24 spatially separated primary tumor and nonmalignant tissues from four treatment-naïve CRC patients. We then used ultra-deep sequencing (17 075× on average) to accurately verify the presence or absence of identified somatic mutations in each sector...
February 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28133913/the-role-of-epithelial-mesenchymal-transition-drivers-zeb1-and-zeb2-in-mediating-docetaxel-resistant-prostate-cancer
#19
Karen Hanrahan, Amanda O'Neill, Maria Prencipe, Jane Bugler, Lisa Murphy, Aurelie Fabre, Martin Puhr, Zoran Culig, Keefe Murphy, R William Watson
Docetaxel is the main treatment for advanced castration-resistant prostate cancer; however, resistance eventually occurs. The development of intratumoral drug-resistant subpopulations possessing a cancer stem cell (CSC) morphology is an emerging mechanism of docetaxel resistance, a process driven by epithelial-mesenchymal transition (EMT). This study characterised EMT in docetaxel-resistant sublines through increased invasion, MMP-1 production and ZEB1 and ZEB2 expression. We also present evidence for differential EMT across PC-3 and DU145 in vitro resistance models as characterised by differential migration, cell colony scattering and susceptibility to the CSC inhibitor salinomycin...
December 19, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28129138/cancer-liquid-biopsy-is-it-ready-for-clinic
#20
Ying Pan, John S Ji, Jason Gang Jin, Winston Patrick Kuo, Hongjun Kang
The management of cancer relies on a combination of imaging and tissue biopsy for diagnosis, monitoring, and molecular classification-based patient stratification to ensure appropriate treatment. Conventional tissue biopsy harvests tumor samples with invasive procedures, which are often difficult for patients with advanced disease. Given the well-recognized intratumor genetic heterogeneity [1], the biopsy of small tumor fragments does not necessarily represent all the genetic aberrations in the tumor, but sampling the entire tumor in each patient is not realistic...
January 2017: IEEE Pulse
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