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Cancer Cell

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https://www.readbyqxmd.com/read/28898700/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#1
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Serkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
No abstract text is available yet for this article.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898699/redefining-hormonal-therapy-for-advanced-prostate-cancer-results-from-the-latitude-and-stampede-studies
#2
Eric J Small
No abstract text is available yet for this article.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898698/enhancing-cd8-t-cell-fatty-acid-catabolism-within%C3%A2-a-metabolically-challenging-tumor-microenvironment-increases-the-efficacy-of-melanoma-immunotherapy
#3
Ying Zhang, Raj Kurupati, Ling Liu, Xiang Yang Zhou, Gao Zhang, Abeer Hudaihed, Flavia Filisio, Wynetta Giles-Davis, Xiaowei Xu, Giorgos C Karakousis, Lynn M Schuchter, Wei Xu, Ravi Amaravadi, Min Xiao, Norah Sadek, Clemens Krepler, Meenhard Herlyn, Gordon J Freeman, Joshua D Rabinowitz, Hildegund C J Ertl
How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and to what degree this affects their ability to combat tumor progression remain poorly understood. Using mouse melanoma models, we report that CD8(+) TILs enhance peroxisome proliferator-activated receptor (PPAR)-α signaling and catabolism of fatty acids (FAs) when simultaneously subjected to hypoglycemia and hypoxia. This metabolic switch partially preserves CD8(+) TILs' effector functions, although co-inhibitor expression increases during tumor progression regardless of CD8(+) TILs' antigen specificity...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898697/chronic-cigarette-smoke-induced-epigenomic-changes-precede-sensitization-of-bronchial-epithelial-cells-to-single-step-transformation-by-kras-mutations
#4
Michelle Vaz, Stephen Y Hwang, Ioannis Kagiampakis, Jillian Phallen, Ashwini Patil, Heather M O'Hagan, Lauren Murphy, Cynthia A Zahnow, Edward Gabrielson, Victor E Velculescu, Hariharan P Easwaran, Stephen B Baylin
We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898696/a-dual-role-of-caspase-8-in-triggering-and-sensing-proliferation-associated-dna-damage-a-key-determinant-of-liver-cancer-development
#5
Yannick Boege, Mohsen Malehmir, Marc E Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K Ahuja, Friederike Böhm, Joachim C Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A Luther, Philipp J Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898695/identification-of-gpc2-as-an-oncoprotein-and-candidate-immunotherapeutic-target-in-high-risk-neuroblastoma
#6
Kristopher R Bosse, Pichai Raman, Zhongyu Zhu, Maria Lane, Daniel Martinez, Sabine Heitzeneder, Komal S Rathi, Nathan M Kendsersky, Michael Randall, Laura Donovan, Sorana Morrissy, Robyn T Sussman, Doncho V Zhelev, Yang Feng, Yanping Wang, Jennifer Hwang, Gonzalo Lopez, Jo Lynne Harenza, Jun S Wei, Bruce Pawel, Tricia Bhatti, Mariarita Santi, Arupa Ganguly, Javed Khan, Marco A Marra, Michael D Taylor, Dimiter S Dimitrov, Crystal L Mackall, John M Maris
We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898694/intravascular-survival-and-extravasation-of-tumor-cells
#7
REVIEW
Boris Strilic, Stefan Offermanns
Most metastasizing tumor cells reach distant sites by entering the circulatory system. Within the bloodstream, they are exposed to severe stress due to loss of adhesion to extracellular matrix, hemodynamic shear forces, and attacks of the immune system, and only a few cells manage to extravasate and to form metastases. We review the current understanding of the cellular and molecular mechanisms that allow tumor cells to survive in the intravascular environment and that mediate and promote tumor cell extravasation...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898693/no-oxygen-no-glucose-no-problem-fatty-acid-catabolism-enhances-effector-cd8-tils
#8
Will Bailis, Justin A Shyer, Michael Chiorazzi, Richard A Flavell
The tumor microenvironment presents metabolic constraints to immunosurveiling cells. In this issue of Cancer Cell, Zhang et al. demonstrate that CD8(+) TILs reprogram under hypoxic and hypoglycemic conditions, regaining effector function by engaging fatty acid catabolism, which is promoted by fenofibrate and synergistic with immune checkpoint blockade therapy.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898692/smoke-induced-changes-to-the-epigenome-provide-fertile-ground-for-oncogenic-mutation
#9
Susan J Clark, Peter L Molloy
How genetic and epigenetic events synergize to generate the oncogenic state is not well understood. In this issue of Cancer Cell, Vaz et al. provide compelling evidence that exposure to chronic cigarette smoke causes progressive epigenetic alterations that prime for key genetic events to drive the development of lung cancer.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898691/leukemic-cells-gas-up-leaky-bone-marrow-blood-vessels
#10
Tomer Itkin, Shahin Rafii
In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898690/when-lmo1-meets-mycn-neuroblastoma-is-metastatic
#11
Zhihui Liu, Carol J Thiele
LMO1 is a high-risk neuroblastoma susceptibility gene, but how LMO1 cooperates with MYCN in neuroblastoma tumorigenesis is unclear. In this issue of Cancer Cell, Zhu et al. develop a novel zebrafish model that elucidates a mechanism by which LMO1 and MYCN synergistically initiate neuroblastoma and contribute to metastatic disease progression.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898689/scratching-the-surface-of-immunotherapeutic-targets-in-neuroblastoma
#12
Clare F Malone, Kimberly Stegmaier
In this issue of Cancer Cell, Bosse et al. report GPC2 as a therapeutic target in neuroblastoma. They show that GPC2 is selectively expressed on the cell surface of neuroblastoma and is a dependency in this disease. Moreover, they demonstrate the therapeutic potential of an antibody-drug conjugate targeting GPC2.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28870739/increased-vascular-permeability-in-the-bone-marrow-microenvironment-contributes-to-disease-progression-and-drug-response-in-acute-myeloid-leukemia
#13
Diana Passaro, Alessandro Di Tullio, Ander Abarrategi, Kevin Rouault-Pierre, Katie Foster, Linda Ariza-McNaughton, Beatriz Montaner, Probir Chakravarty, Leena Bhaw, Giovanni Diana, François Lassailly, John Gribben, Dominique Bonnet
The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28867147/lmo1-synergizes-with-mycn-to-promote-neuroblastoma-initiation-and-metastasis
#14
Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Zhiwei Dong, Cheng Zhang, Gonzalo Lopez, Ting Tao, Shuning He, Andrew C Wood, Derek Oldridge, Choong Yong Ung, Janine H van Ree, Amish Khan, Brittany M Salazar, Edroaldo Lummertz da Rocha, Mark W Zimmerman, Feng Guo, Hong Cao, Xiaonan Hou, S John Weroha, Antonio R Perez-Atayde, Donna S Neuberg, Alexander Meves, Mark A McNiven, Jan M van Deursen, Hu Li, John M Maris, A Thomas Look
A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28810149/o2-%C3%A2-and-h2o2-mediated-disruption-of-fe-metabolism-causes-the-differential-susceptibility-of-nsclc-and-gbm-cancer-cells-to-pharmacological-ascorbate
#15
Joshua D Schoenfeld, Zita A Sibenaller, Kranti A Mapuskar, Brett A Wagner, Kimberly L Cramer-Morales, Muhammad Furqan, Sonia Sandhu, Thomas L Carlisle, Mark C Smith, Taher Abu Hejleh, Daniel J Berg, Jun Zhang, John Keech, Kalpaj R Parekh, Sudershan Bhatia, Varun Monga, Kellie L Bodeker, Logan Ahmann, Sandy Vollstedt, Heather Brown, Erin P Shanahan Kauffman, Mary E Schall, Ray J Hohl, Gerald H Clamon, Jeremy D Greenlee, Matthew A Howard, Michael K Schultz, Brian J Smith, Dennis P Riley, Frederick E Domann, Joseph J Cullen, Garry R Buettner, John M Buatti, Douglas R Spitz, Bryan G Allen
No abstract text is available yet for this article.
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28810148/choose-and-use-your-chemical-probe-wisely-to-explore-cancer-biology
#16
Julian Blagg, Paul Workman
No abstract text is available yet for this article.
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28810147/macrophage-polarization-contributes-to-glioblastoma-eradication-by-combination-immunovirotherapy-and-immune-checkpoint-blockade
#17
Dipongkor Saha, Robert L Martuza, Samuel D Rabkin
Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cured most mice in two glioma models...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28810146/swarm-intelligence-enhanced-detection-of-non-small-cell-lung-cancer-using-tumor-educated-platelets
#18
Myron G Best, Nik Sol, Sjors G J G In 't Veld, Adrienne Vancura, Mirte Muller, Anna-Larissa N Niemeijer, Aniko V Fejes, Lee-Ann Tjon Kon Fat, Anna E Huis In 't Veld, Cyra Leurs, Tessa Y Le Large, Laura L Meijer, Irsan E Kooi, François Rustenburg, Pepijn Schellen, Heleen Verschueren, Edward Post, Laurine E Wedekind, Jillian Bracht, Michelle Esenkbrink, Leon Wils, Francesca Favaro, Jilian D Schoonhoven, Jihane Tannous, Hanne Meijers-Heijboer, Geert Kazemier, Elisa Giovannetti, Jaap C Reijneveld, Sander Idema, Joep Killestein, Michal Heger, Saskia C de Jager, Rolf T Urbanus, Imo E Hoefer, Gerard Pasterkamp, Christine Mannhalter, Jose Gomez-Arroyo, Harm-Jan Bogaard, David P Noske, W Peter Vandertop, Daan van den Broek, Bauke Ylstra, R Jonas A Nilsson, Pieter Wesseling, Niki Karachaliou, Rafael Rosell, Elizabeth Lee-Lewandrowski, Kent B Lewandrowski, Bakhos A Tannous, Adrianus J de Langen, Egbert F Smit, Michel M van den Heuvel, Thomas Wurdinger
Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28810145/integrative-analysis-identifies-four-molecular-and-clinical-subsets-in-uveal-melanoma
#19
A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman
Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28810144/integrated-genomic-characterization-of-pancreatic-ductal-adenocarcinoma
#20
(no author information available yet)
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations...
August 14, 2017: Cancer Cell
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