Log in to search using one of your social media accounts:

 

Correction: A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer
(Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research

Correction: SSRP1 Cooperates with PARP and XRCC1 to Facilitate Single-Strand DNA Break Repair by Chromatin Priming
(Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research

Cross-Cancer Analysis Reveals Novel Pleiotropic Associations—Response
(Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Rayjean J. Hung, Gordon Fehringer, Graham Casey, Stephen B. Gruber, Ulrike Peters, Ellen L. Goode, Thomas A. Sellers, Christopher A. Haiman, David J. Hunter, Peter Kraft, Christopher I. Amos, Matthew L. Freedman, Michael D. Wilson Tags: Letter to the Editor Source Type: research

Cross-Cancer Analysis Reveals Novel Pleiotropic Associations—Letter
(Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Lei Quan, Alan Hutson, Peter Demant Tags: Letter to the Editor Source Type: research

Diabetes Treatments and Risks of Adverse Breast Cancer Outcomes among Early-Stage Breast Cancer Patients: A SEER-Medicare Analysis
In this study, we conducted a retrospective cohort study using the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Women were included in the study if they were aged 66 to 80 years, newly diagnosed with stage I or II breast cancer, and enrolled in Medicare Parts A, B, and D during 2007 to 2011. Information on dispensed diabetes-related medications was obtained from Medicare Part D claims data. Our primary outcomes were second breast cancer events (SBCE), breast cancer recurrence, and breast cancer death. Time-varying Cox proportional hazard models were used to estimate HRs and their 95% confide...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Lu Chen, Jessica Chubak, Denise M. Boudreau, William E. Barlow, Noel S. Weiss, Christopher I. Li Tags: Prevention and Epidemiology Source Type: research

Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy
Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with common...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Yang Zhao, Chenran Zhang, Liquan Gao, Xinhe Yu, Jianhao Lai, Dehua Lu, Rui Bao, Yanpu Wang, Bing Jia, Fan Wang, Zhaofei Liu Tags: Integrated Systems and Technologies Source Type: research

Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids
In this study, we established a label-free, noninvasive optical coherence tomography (OCT) imaging platform to characterize 3D morphologic and physiologic information of multicellular tumor spheroids (MCTS) growing from approximately 250 to 600 μm in height over 21 days. In particular, tumor spheroids of two cell lines, glioblastoma (U-87MG) and colorectal carcinoma (HCT116), exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calc...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Yongyang Huang, Shunqiang Wang, Qiongyu Guo, Sarah Kessel, Ian Rubinoff, Leo Li-Ying Chan, Peter Li, Yaling Liu, Jean Qiu, Chao Zhou Tags: Integrated Systems and Technologies Source Type: research

Transplantation of iPS-Derived Tumor Cells with a Homozygous MHC Haplotype Induces GRP94 Antibody Production in MHC-Matched Macaques
In this study, we demonstrate that autoantibodies can mitigate tumor growth in vitro and in vivo. We generated two cancer cell lines, embryonal carcinoma and glioblastoma cell lines, from monkey-induced pluripotent stem cells (iPSC) carrying a homozygous haplotype of major histocompatibility complex (MHC, Mafa in Macaca fascicularis). To establish a monkey cancer model, we transplanted these cells into monkeys carrying the matched Mafa haplotype in one of the chromosomes. Neither Mafa-homozygous cancer cell line grew in monkeys carrying the matched Mafa haplotype heterozygously. We detected in the plasma of these monkeys a...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Hirohito Ishigaki, Toshinaga Maeda, Hirokazu Inoue, Tsuyoshi Akagi, Takako Sasamura, Hideaki Ishida, Toshiro Inubushi, Junko Okahara, Takashi Shiina, Misako Nakayama, Yasushi Itoh, Kazumasa Ogasawara Tags: Microenvironment and Immunology Source Type: research

Anti-CD137 Suppresses Tumor Growth by Blocking Reverse Signaling by CD137 Ligand
CD137 (4-1BB) is a T-cell costimulatory molecule, and agonstic CD137 antibodies are currently being evaluated in the clinic as cancer immunotherapy. Recently, it was found that CD137−/− mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here, we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results. Specifically, CD137L suppressed intratumoral differentiation of IL12-producing CD103+ DC and...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Sang W. Kang, Sang C. Lee, So H. Park, Juyang Kim, Hyeon H. Kim, Hyeon-Woo Lee, Su K. Seo, Byoung S. Kwon, Hong R. Cho, Byungsuk Kwon Tags: Microenvironment and Immunology Source Type: research

Tenascin-C and Integrin {alpha}9 Mediate Interactions of Prostate Cancer with the Bone Microenvironment
Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here, we report that tenascin C is expressed in the bone endosteum and is associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. In addition, metastatic cells preferentially migrated and colonized tenascin-C–coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Rebeca San Martin, Ravi Pathak, Antrix Jain, Sung Yun Jung, Susan G. Hilsenbeck, Maria C. Pina–Barba, Andrew G. Sikora, Kenneth J. Pienta, David R. Rowley Tags: Microenvironment and Immunology Source Type: research

Enhanced Acid Sphingomyelinase Activity Drives Immune Evasion and Tumor Growth in Non-Small Cell Lung Carcinoma
In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non–small cell lung cancer (NSCLC). RNAi-mediated attenuation of SMPD1 in human NSCLC cells rendered them resistant to serum starvation–induced apoptosis. In a murine model of lung adenocarcinoma, ASM deficiency reduced tumor development in a manner associated with significant enhancement of Th1-mediated and cytotoxic T-cell–mediated antitumor immunity. Our findings indicate that targeting ASM in NSCLC can act by tumor cell–intrinsic and –extrinsic mechanisms to suppress tumor cel...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Katerina Kachler, Maximilian Bailer, Lisanne Heim, Fabian Schumacher, Martin Reichel, Corinna D. Holzinger, Sonja Trump, Susanne Mittler, Juliana Monti, Denis I. Trufa, Ralf J. Rieker, Arndt Hartmann, Horia Sirbu, Burkhard Kleuser, Johannes Kornhuber, Sus Tags: Microenvironment and Immunology Source Type: research

Gemcitabine-Induced TIMP1 Attenuates Therapy Response and Promotes Tumor Growth and Liver Metastasis in Pancreatic Cancer
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in preclinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using bot...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Zenobia D'Costa, Keaton Jones, Abul Azad, Ruud van Stiphout, Su Y. Lim, Ana L. Gomes, Paul Kinchesh, Sean C. Smart, W. Gillies McKenna, Francesca M. Buffa, Owen J. Sansom, Ruth J. Muschel, Eric O'Neill, Emmanouil Fokas Tags: Microenvironment and Immunology Source Type: research

Tethering IL2 to Its Receptor IL2R{beta} Enhances Antitumor Activity and Expansion of Natural Killer NK92 Cells
IL2 is an immunostimulatory cytokine for key immune cells including T cells and natural killer (NK) cells. Systemic IL2 supplementation could enhance NK-mediated immunity in a variety of diseases ranging from neoplasms to viral infection. However, its systemic use is restricted by its serious side effects and limited efficacy due to activation of T regulatory cells (Tregs). IL2 signaling is mediated through interactions with a multi-subunit receptor complex containing IL2Rα, IL2Rβ, and IL2Rγ. Adult natural killer (NK) cells express only IL2Rβ and IL2Rγ subunits and are therefore relatively insen...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Youssef Jounaidi, Joseph F. Cotten, Keith W. Miller, Stuart A. Forman Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

Caveolae-Mediated Endocytosis Is Critical for Albumin Cellular Uptake and Response to Albumin-Bound Chemotherapy
This study addresses this gap in knowledge by identifying that caveolin-1 (Cav-1) is a candidate mechanism-based biomarker. Caveolae are small membrane invaginations important for transendothelial albumin uptake. Cav-1, the principal structural component of caveolae, is overexpressed in the cancers noted above that respond to nab-paclitaxel. Thus, we hypothesized that Cav-1 may be critical for albumin uptake in tumors and perhaps determine their response to this drug. Cav-1 protein levels correlated positively with nab-paclitaxel sensitivity. RNAi-mediated attenuation of Cav-1 expression reduced uptake of albumin and nab-p...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Moumita Chatterjee, Edgar Ben-Josef, Ryan Robb, Marall Vedaie, Star Seum, Krishnan Thirumoorthy, Kamalakannan Palanichamy, Matthew Harbrecht, Arnab Chakravarti, Terence M. Williams Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy
In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux. AZD3965 also increased the levels of TCA cycle–related metabolites and 13C-glucose mitochondrial metabolism, enhancing oxidative pyruvate dehydrogenase and anaplerotic pyruvate carboxylase fluxes. Increased mitochondrial metabolism was necessary to maintain cell survival under drug stress. These effects were counteracted by coadministr...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markella Koniordou, Harold G. Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R. Eykyn, Paul D. Smith, Martin O. Leach Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

KDM4 Inhibition Targets Breast Cancer Stem-like Cells
Traditional treatments for breast cancer fail to address therapy-resistant cancer stem–like cells that have been characterized by changes in epigenetic regulators such as the lysine demethylase KDM4. Here, we describe an orally available, selective and potent KDM4 inhibitor (QC6352) with unique preclinical characteristics. To assess the antitumor properties of QC6352, we established a method to isolate and propagate breast cancer stem–like cells (BCSC) from individual triple-negative tumors resected from patients after neoadjuvant chemotherapy. Limiting-dilution orthotopic xenografts of these BCSCs regenerated ...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Eric Metzger, Stella S. Stepputtis, Juliane Strietz, Bogdan–Tiberius Preca, Sylvia Urban, Dominica Willmann, Anita Allen, Fides Zenk, Nicola Iovino, Peter Bronsert, Amelie Proske, Marie Follo, Melanie Boerries, Elmar Stickeler, Jiangchun Xu, Michael Tags: Tumor and Stem Cell Biology Source Type: research

FSTL1 Promotes Metastasis and Chemoresistance in Esophageal Squamous Cell Carcinoma through NF{kappa}B-BMP Signaling Cross-talk
Esophageal squamous cell carcinoma (ESCC) has a generally poor prognosis, and molecular markers to improve early detection and predict outcomes are greatly needed. Here, we report that the BMP-binding follistatin-like protein FSTL1 is overexpressed in ESCCs, where it correlates with poor overall survival. Genetic amplification of FSTL1 or chromosome 3q, where it is located, occurred frequently in ESCC, where FSTL1 copy number correlated positively with higher FSTL1 protein expression. Elevating FSTL1 levels by various means was sufficient to drive ESCC cell proliferation, clonogenicity, migration, invasion, self-renewal, a...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Marco Chi-Chung Lau, Kai Yu Ng, Tin Lok Wong, Man Tong, Terence K. Lee, Xiao-Yan Ming, Simon Law, Nikki P. Lee, Annie L. Cheung, Yan-Ru Qin, Kwok Wah Chan, Wen Ning, Xin-Yuan Guan, Stephanie Ma Tags: Tumor and Stem Cell Biology Source Type: research

ATG5 Mediates a Positive Feedback Loop between Wnt Signaling and Autophagy in Melanoma
In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin. To define the physiologic relevance of this loop, melanoma cells with different Wnt status were treated in vitro and in vivo with the potent lysosomotropic compound Lys05. Wn...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Abibatou Ndoye, Anna Budina-Kolomets, Curtis H. Kugel III, Marie R. Webster, Amanpreet Kaur, Reeti Behera, Vito W. Rebecca, Ling Li, Patricia A. Brafford, Qin Liu, Y.N. Vashisht Gopal, Michael A. Davies, Gordon B. Mills, Xiaowei Xu, Hong Wu, Meenhard Herl Tags: Tumor and Stem Cell Biology Source Type: research

Novel SEC61G-EGFR Fusion Gene in Pediatric Ependymomas Discovered by Clonal Expansion of Stem Cells in Absence of Exogenous Mitogens
This study suggests a basis for this phenomenon in the selection for mitogen-independent (MI) stem-like cells with impaired proliferation but increased intracranial tumorigenicity. MI ependymoma cell lines created by selection for EGF/FGF2-independent proliferation exhibited constitutive activation of EGFR, AKT, and STAT3 and sensitization to the antiproliferative effects of EGFR tyrosine kinase inhibitors (TKI). One highly tumorigenic MI line harbored membrane-bound, constitutively active, truncated EGFR. Two EGFR mutants (ΔN566 and ΔN599) were identified as products of intrachromosomal rearrangements fusing t...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Tiziana Servidei, Daniela Meco, Valentina Muto, Alessandro Bruselles, Andrea Ciolfi, Nadia Trivieri, Matteo Lucchini, Roberta Morosetti, Massimiliano Mirabella, Maurizio Martini, Massimo Caldarelli, Anna Lasorella, Marco Tartaglia, Riccardo Riccardi Tags: Tumor and Stem Cell Biology Source Type: research

Lysyl Oxidase-like Protein LOXL2 Promotes Lung Metastasis of Breast Cancer
The lysyl oxidase–like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LO...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Fernando Salvador, Alberto Martin, Celia Lopez–Menendez, Gema Moreno–Bueno, Vanesa Santos, Alberto Vazquez–Naharro, Patricia G. Santamaria, Saleta Morales, Pierre R. Dubus, Laura Muinelo–Romay, Rafael Lopez–Lopez, Jason C. Tu Tags: Tumor and Stem Cell Biology Source Type: research

ANGPTL1 Interacts with Integrin {alpha}1{beta}1 to Suppress HCC Angiogenesis and Metastasis by Inhibiting JAK2/STAT3 Signaling
Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). Here, we report that downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis, and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivo tumorigenicity, cell motility, and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2–mediated antiapoptotic pathway and decreased cell migration and in...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Qian Yan, Lingxi Jiang, Ming Liu, Dandan Yu, Yu Zhang, Yan Li, Shuo Fang, , Ying-Hui Zhu, Yun-Fei Yuan, Xin-Yuan Guan Tags: Tumor and Stem Cell Biology Source Type: research

KIT Suppresses BRAFV600E-Mutant Melanoma by Attenuating Oncogenic RAS/MAPK Signaling
The receptor tyrosine kinase KIT promotes survival and migration of melanocytes during development, and excessive KIT activity hyperactivates the RAS/MAPK pathway and can drive formation of melanomas, most notably of rare melanomas that occur on volar and mucosal surfaces of the skin. The much larger fraction of melanomas that occur on sun-exposed skin is driven primarily by BRAF- or NRAS-activating mutations, but these melanomas exhibit a surprising loss of KIT expression, which raises the question of whether loss of KIT in these tumors facilitates tumorigenesis. To address this question, we introduced a kit(lf) mutation ...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: James V. Neiswender, Robert L. Kortum, Caitlin Bourque, Melissa Kasheta, Leonard I. Zon, Deborah K. Morrison, Craig J. Ceol Tags: Tumor and Stem Cell Biology Source Type: research

Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587
Tumor–stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-supp...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Javier Figueroa, Lynette M. Phillips, Tal Shahar, Anwar Hossain, Joy Gumin, Hoon Kim, Andrew J. Bean, George A. Calin, Juan Fueyo, Edgar T. Walters, Raghu Kalluri, Roel G. Verhaak, Frederick F. Lang Tags: Tumor and Stem Cell Biology Source Type: research

Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation
Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels of glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion to acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response to complex energetic, enzymatic, and metabolic cues. Here we utilized a mouse model of hepatocyte-specific PDC inactivation to determine the need for this metabolic link during normal hepatocyte regeneration and malignant transformation. In PDC &...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Laura E. Jackson, Sucheta Kulkarni, Huabo Wang, Jie Lu, James M. Dolezal, Sivakama S. Bharathi, Sarangarajan Ranganathan, Mulchand S. Patel, Rahul Deshpande, Frances Alencastro, Stacy G. Wendell, Eric S. Goetzman, Andrew W. Duncan, Edward V. Prochownik Tags: Molecular and Cellular Pathobiology Source Type: research

MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway
Long noncoding RNAs (lncRNA) participate in carcinogenesis and tumor progression in lung cancer. Here, we report the identification of a lncRNA signature associated with metastasis of non–small cell lung cancer (NSCLC). In particular, elevated expression of LINC00963 (MetaLnc9) in human NSCLC specimens correlated with poor prognosis, promoted migration and invasion of NSCLC cells in vitro, and enhanced lung metastasis formation in vivo. Mechanistic investigations showed that MetaLnc9 interacted with the glycolytic kinase PGK1 and prevented its ubiquitination in NSCLC cells, leading to activation of the oncogenic AKT/...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Tao Yu, Yingjun Zhao, Zhixiang Hu, Jing Li, Dandan Chu, Jiwei Zhang, Zhe Li, Bing Chen, Xiao Zhang, Hongyu Pan, Shengli Li, Hechun Lin, Lei Liu, Mingxia Yan, Xianghuo He, Ming Yao Tags: Molecular and Cellular Pathobiology Source Type: research

YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63-GPX2 Axis and ROS Accumulation
Lung squamous cell carcinoma (SCC), accounting for approximately 30% of non–small cell lung cancer, is often refractory to therapy. Screening a small-molecule library, we identified digitoxin as a high potency compound for suppressing human lung SCC growth in vitro and in vivo. Mechanistic investigations revealed that digitoxin attenuated YAP phosphorylation and promoted YAP nuclear sequestration. YAP activation led to excessive accumulation of reactive oxygen species (ROS) by downregulating the antioxidant enzyme GPX2 in a manner related to p63 blockade. In patient-derived xenograft models, digitoxin treatment effic...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Hsinyi Huang, Wenjing Zhang, Yafang Pan, Yijun Gao, Lei Deng, Fuming Li, Fei Li, Xueyan Ma, Shenda Hou, Jing Xu, Peixue Li, Xiaoxun Li, Guohong Hu, Cheng Li, Haiquan Chen, Lei Zhang, Hongbin Ji Tags: Molecular and Cellular Pathobiology Source Type: research

PADI2-Mediated Citrullination Promotes Prostate Cancer Progression
Onset of castration-resistance prostate cancer (CRPC) after long-term androgen deprivation therapy remains a major obstacle in the treatment of prostate cancer. The peptidylarginine deiminase PADI2 has been implicated in chronic inflammatory diseases and cancer. Here we show that PADI2 is an androgen-repressed gene and is upregulated in CRPC. PADI2 expression was required for survival and cell-cycle progression of prostate cancer cells, and PADI2 promoted proliferation of prostate cancer cells under androgen-deprived or castration conditions in vitro and in vivo. Cytoplasmic PADI2 protected the androgen receptor (AR) again...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Lin Wang, Guanhua Song, Xiang Zhang, Tingting Feng, Jihong Pan, Weiwen Chen, Muyi Yang, Xinnuo Bai, Yu Pang, Jindan Yu, Jinxiang Han, Bo Han Tags: Molecular and Cellular Pathobiology Source Type: research

Upregulation of Cystathionine-{beta}-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis
The trans-sulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells. Dif...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Ches'Nique M. Phillips, John R. Zatarain, Michael E. Nicholls, Craig Porter, Steve G. Widen, Ketan Thanki, Paul Johnson, Muhammad U. Jawad, Mary P. Moyer, James W. Randall, Judith L. Hellmich, Manȷit Maskey, Suimin Qiu, Thomas G. Wood, Nadiya Druzh Tags: Molecular and Cellular Pathobiology Source Type: research

miR-193b-Regulated Signaling Networks Serve as Tumor Suppressors in Liposarcoma and Promote Adipogenesis in Adipose-Derived Stem Cells
In this study, we evaluated the functions of miRNA (miR-193b) in liposarcoma in vitro and in vivo. Deep RNA sequencing on 93 WDLS, 145 DDLS, and 12 normal fat samples demonstrated that miR-193b was significantly underexpressed in DDLS compared with normal fat. Reintroduction of miR-193b induced apoptosis in liposarcoma cells and promoted adipogenesis in human adipose-derived stem cells (ASC). Integrative transcriptomic and proteomic analysis of miR-193b–target networks identified novel direct targets, including CRK-like proto-oncogene (CRKL) and focal adhesion kinase (FAK). miR-193b was found to regulate FAK–SR...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Ying Z. Mazzu, Yulan Hu, Rajesh K. Soni, Kelly M. Mojica, Li-Xuan Qin, Phaedra Agius, Zachary M. Waxman, Aleksandra Mihailovic, Nicholas D. Socci, Ronald C. Hendrickson, Thomas Tuschl, Samuel Singer Tags: Molecular and Cellular Pathobiology Source Type: research

Discovery of Human-Similar Gene Fusions in Canine Cancers
This study demonstrates similar gene fusion partners and mechanisms in human–dog corresponding tumors and allows for selection of targeted therapies in preclinical and clinical trials with pet dogs prior to human trials, within the framework of personalized medicine. Cancer Res; 77(21); 5721–7. ©2017 AACR. (Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Ronan Ulve, Melanie Rault, Mathieu Bahin, Laetitia Lagoutte, Jerome Abadie, Clotilde De Brito, Jean–Michel Coindre, Nadine Botherel, Audrey Rousseau, Valentin Wucher, Edouard Cadieu, Catherine Thieblemont, Christophe Hitte, Laurence Cornevin, Floria Tags: Priority Report Source Type: research

Moonshot Acceleration Factor: Medical Imaging
Medical imaging is essential to screening, early diagnosis, and monitoring responses to cancer treatments and, when used with other diagnostics, provides guidance for clinicians in choosing the most effective patient management plan that maximizes survivorship and quality of life. At a gathering of agency officials, patient advocacy organizations, industry/professional stakeholder groups, and clinical/basic science academicians, recommendations were made on why and how one should build a “cancer knowledge network” that includes imaging. Steps to accelerate the translation and clinical adoption of cancer discove...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Eva M. Sevick-Muraca, Richard A. Frank, Maryellen L. Giger, James L. Mulshine Tags: Meeting Report Source Type: research

Meiosis-like Functions in Oncogenesis: A New View of Cancer
Cancer cells have many abnormal characteristics enabling tumors to grow, spread, and avoid immunologic and therapeutic destruction. Central to this is the innate ability of populations of cancer cells to rapidly evolve. One feature of many cancers is that they activate genes that are normally associated with distinct developmental states, including germ cell–specific genes. This has historically led to the proposal that tumors take on embryonal characteristics, the so called embryonal theory of cancer. However, one group of germline genes, not directly associated with embryonic somatic tissue genesis, is the one that...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Ramsay J. McFarlane, Jane A. Wakeman Tags: Perspective Source Type: research

A Collaborative Model for Accelerating the Discovery and Translation of Cancer Therapies
Preclinical studies using genetically engineered mouse models (GEMM) have the potential to expedite the development of effective new therapies; however, they are not routinely integrated into drug development pipelines. GEMMs may be particularly valuable for investigating treatments for less common cancers, which frequently lack alternative faithful models. Here, we describe a multicenter cooperative group that has successfully leveraged the expertise and resources from philanthropic foundations, academia, and industry to advance therapeutic discovery and translation using GEMMs as a preclinical platform. This effort, know...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Ophelia Maertens, Mila E. McCurrach, Benȷamin S. Braun, Thomas De Raedt, Inbal Epstein, Tannie Q. Huang, Jennifer O. Lauchle, Hyerim Lee, Jianqiang Wu, Timothy P. Cripe, D. Wade Clapp, Nancy Ratner, Kevin Shannon, Karen Cichowski Tags: Reviews Source Type: research

Therapeutic Targeting of Oncogenic Tyrosine Phosphatases
Protein tyrosine phosphatases (PTP) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTK) in controlling cellular homeostasis. Given the activating role that some PTKs play in initiating growth factor–mediated cellular processes, PTPs are usually perceived as the negative regulators of these events and therefore tumor suppressive in nature. However, mounting evidence indicate that PTPs do not always antagonize the activity of PTKs in regulating tyrosine phosphorylation, but can also play dominant roles in the initiation and progression of signaling cascades ...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Rochelle Frankson, Zhi-Hong Yu, Yunpeng Bai, Qinglin Li, Ruo-Yu Zhang, Zhong-Yin Zhang Tags: Reviews Source Type: research

Highlights from Recent Cancer Literature
(Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Tags: Breaking Advances Source Type: research

“Personalized Cancer Therapy”: A Publicly Available Precision Oncology Resource
High-throughput genomic and molecular profiling of tumors is emerging as an important clinical approach. Molecular profiling is increasingly being used to guide cancer patient care, especially in advanced and incurable cancers. However, navigating the scientific literature to make evidence-based clinical decisions based on molecular profiling results is overwhelming for many oncology clinicians and researchers. The Personalized Cancer Therapy website (www.personalizedcancertherapy.org) was created to provide an online resource for clinicians and researchers to facilitate navigation of available data. Specifically, this res...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Katherine C. Kurnit, Ann M. Bailey, Jia Zeng, Amber M. Johnson, Md. Abu Shufean, Lauren Brusco, Beate C. Litzenburger, Nora S. Sanchez, Yekaterina B. Khotskaya, Viȷaykumar Holla, Amy Simpson, Gordon B. Mills, John Mendelsohn, Elmer Bernstam, Kenna Tags: Focus on Computer Resources Source Type: research

LesionTracker: Extensible Open-Source Zero-Footprint Web Viewer for Cancer Imaging Research and Clinical Trials
Oncology clinical trials have become increasingly dependent upon image-based surrogate endpoints for determining patient eligibility and treatment efficacy. As therapeutics have evolved and multiplied in number, the tumor metrics criteria used to characterize therapeutic response have become progressively more varied and complex. The growing intricacies of image-based response evaluation, together with rising expectations for rapid and consistent results reporting, make it difficult for site radiologists to adequately address local and multicenter imaging demands. These challenges demonstrate the need for advanced cancer i...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Trinity Urban, Erik Ziegler, Rob Lewis, Chris Hafey, Cheryl Sadow, Annick D. Van den Abbeele, Gordon J. Harris Tags: Focus on Computer Resources Source Type: research

DeepPhe: A Natural Language Processing System for Extracting Cancer Phenotypes from Clinical Records
Precise phenotype information is needed to understand the effects of genetic and epigenetic changes on tumor behavior and responsiveness. Extraction and representation of cancer phenotypes is currently mostly performed manually, making it difficult to correlate phenotypic data to genomic data. In addition, genomic data are being produced at an increasingly faster pace, exacerbating the problem. The DeepPhe software enables automated extraction of detailed phenotype information from electronic medical records of cancer patients. The system implements advanced Natural Language Processing and knowledge engineering methods wit...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Guergana K. Savova, Eugene Tseytlin, Sean Finan, Melissa Castine, Timothy Miller, Olga Medvedeva, David Harris, Harry Hochheiser, Chen Lin, Girish Chavan, Rebecca S. Jacobson Tags: Focus on Computer Resources Source Type: research

TumorMap: Exploring the Molecular Similarities of Cancer Samples in an Interactive Portal
Vast amounts of molecular data are being collected on tumor samples, which provide unique opportunities for discovering trends within and between cancer subtypes. Such cross-cancer analyses require computational methods that enable intuitive and interactive browsing of thousands of samples based on their molecular similarity. We created a portal called TumorMap to assist in exploration and statistical interrogation of high-dimensional complex “omics” data in an interactive and easily interpretable way. In the TumorMap, samples are arranged on a hexagonal grid based on their similarity to one another in the orig...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Yulia Newton, Adam M. Novak, Teresa Swatloski, Duncan C. McColl, Sahil Chopra, Kiley Graim, Alana S. Weinstein, Robert Baertsch, Sofie R. Salama, Kyle Ellrott, Manu Chopra, Theodore C. Goldstein, David Haussler, Olena Morozova, Joshua M. Stuart Tags: Focus on Computer Resources Source Type: research

TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells
Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor–immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor–immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactiv...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Taiwen Li, Jingyu Fan, Binbin Wang, Nicole Traugh, Qianming Chen, Jun S. Liu, Bo Li, X. Shirley Liu Tags: Focus on Computer Resources Source Type: research

Computational Radiomics System to Decode the Radiographic Phenotype
Radiomics aims to quantify phenotypic characteristics on medical imaging through the use of automated algorithms. Radiomic artificial intelligence (AI) technology, either based on engineered hard-coded algorithms or deep learning methods, can be used to develop noninvasive imaging-based biomarkers. However, lack of standardized algorithm definitions and image processing severely hampers reproducibility and comparability of results. To address this issue, we developed PyRadiomics, a flexible open-source platform capable of extracting a large panel of engineered features from medical images. PyRadiomics is implemented in Pyt...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Joost J.M. van Griethuysen, Andriy Fedorov, Chintan Parmar, Ahmed Hosny, Nicole Aucoin, Vivek Narayan, Regina G.H. Beets-Tan, Jean-Christophe Fillion-Robin, Steve Pieper, Hugo J.W.L. Aerts Tags: Focus on Computer Resources Source Type: research

SlicerDMRI: Open Source Diffusion MRI Software for Brain Cancer Research
We describe SlicerDMRI, a software suite that enables visualization and analysis of dMRI for neuroscientific studies and patient-specific anatomic assessment. SlicerDMRI has been successfully applied in multiple studies of the human brain in health and disease, and here, we especially focus on its cancer research applications. As an extension module of the 3D Slicer medical image computing platform, the SlicerDMRI suite enables dMRI analysis in a clinically relevant multimodal imaging workflow. Core SlicerDMRI functionality includes diffusion tensor estimation, white matter tractography with single and multi-fiber models, ...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Isaiah Norton, Walid Ibn Essayed, Fan Zhang, Sonia Pujol, Alex Yarmarkovich, Alexandra J. Golby, Gordon Kindlmann, Demian Wasserman, Raul San Jose Estepar, Yogesh Rathi, Steve Pieper, Ron Kikinis, Hans J. Johnson, Carl-Fredrik Westin, Lauren J. O'Donnell Tags: Focus on Computer Resources Source Type: research

Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis
In this study, we present an integrative genomics framework for constructing a prognostic model for clear cell renal cell carcinoma. We used patient data from The Cancer Genome Atlas (n = 410), extracting hundreds of cellular morphologic features from digitized whole-slide images and eigengenes from functional genomics data to predict patient outcome. The risk index generated by our model correlated strongly with survival, outperforming predictions based on considering morphologic features or eigengenes separately. The predicted risk index also effectively stratified patients in early-stage (stage I and stage II) tumors, w...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Jun Cheng, Jie Zhang, Yatong Han, Xusheng Wang, Xiufen Ye, Yuebo Meng, Anil Parwani, Zhi Han, Qianjin Feng, Kun Huang Tags: Focus on Computer Resources Source Type: research

dcmqi: An Open Source Library for Standardized Communication of Quantitative Image Analysis Results Using DICOM
Quantitative analysis of clinical image data is an active area of research that holds promise for precision medicine, early assessment of treatment response, and objective characterization of the disease. Interoperability, data sharing, and the ability to mine the resulting data are of increasing importance, given the explosive growth in the number of quantitative analysis methods being proposed. The Digital Imaging and Communications in Medicine (DICOM) standard is widely adopted for image and metadata in radiology. dcmqi (DICOM for Quantitative Imaging) is a free, open source library that implements conversion of the dat...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Christian Herz, Jean–Christophe Fillion–Robin, Michael Onken, Jorg Riesmeier, Andras Lasso, Csaba Pinter, Gabor Fichtinger, Steve Pieper, David Clunie, Ron Kikinis, Andriy Fedorov Tags: Focus on Computer Resources Source Type: research

An Image Analysis Resource for Cancer Research: PIIP—Pathology Image Informatics Platform for Visualization, Analysis, and Management
This article describes the viewing software and the mechanism to extend functionality by plugins, brief descriptions of which are provided as examples, to guide users who want to use this platform. PIIP project materials, including a video describing its usage and applications, and links for the Sedeen Viewer, plug-ins, and user manuals are freely available through the project web page: http://pathiip.org. Cancer Res; 77(21); e83–86. ©2017 AACR. (Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Anne L. Martel, Dan Hosseinzadeh, Caglar Senaras, Yu Zhou, Azadeh Yazdanpanah, Rushin Shojaii, Emily S. Patterson, Anant Madabhushi, Metin N. Gurcan Tags: Focus on Computer Resources Source Type: research

A Containerized Software System for Generation, Management, and Exploration of Features from Whole Slide Tissue Images
This article describes a suite of services and web applications that allow users to select regions of interest in whole slide tissue images, run a segmentation pipeline on the selected regions to extract nuclei and compute shape, size, intensity, and texture features, store and index images and analysis results, and visualize and explore images and computed features. All the services are deployed as containers and the user-facing interfaces as web-based applications. The set of containers and web applications presented in this article is used in cancer research studies of morphologic characteristics of tumor tissues. The s...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Joel Saltz, Ashish Sharma, Ganesh Iyer, Erich Bremer, Feiqiao Wang, Alina Jasniewski, Tammy DiPrima, Jonas S. Almeida, Yi Gao, Tianhao Zhao, Mary Saltz, Tahsin Kurc Tags: Focus on Computer Resources Source Type: research

The Digital Slide Archive: A Software Platform for Management, Integration, and Analysis of Histology for Cancer Research
Tissue-based cancer studies can generate large amounts of histology data in the form of glass slides. These slides contain important diagnostic, prognostic, and biological information and can be digitized into expansive and high-resolution whole-slide images using slide-scanning devices. Effectively utilizing digital pathology data in cancer research requires the ability to manage, visualize, share, and perform quantitative analysis on these large amounts of image data, tasks that are often complex and difficult for investigators with the current state of commercial digital pathology software. In this article, we describe ...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: David A. Gutman, Mohammed Khalilia, Sanghoon Lee, Michael Nalisnik, Zach Mullen, Jonathan Beezley, Deepak R. Chittajallu, David Manthey, Lee A.D. Cooper Tags: Focus on Computer Resources Source Type: research

Platform for Quantitative Evaluation of Spatial Intratumoral Heterogeneity in Multiplexed Fluorescence Images
We introduce THRIVE (Tumor Heterogeneity Research Interactive Visualization Environment), an open-source tool developed to assist cancer researchers in interactive hypothesis testing. The focus of this tool is to quantify spatial intratumoral heterogeneity (ITH), and the interactions between different cell phenotypes and noncellular constituents. Specifically, we foresee applications in phenotyping cells within tumor microenvironments, recognizing tumor boundaries, identifying degrees of immune infiltration and epithelial/stromal separation, and identification of heterotypic signaling networks underlying microdomains. The ...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Daniel M. Spagnolo, Yousef Al-Kofahi, Peihong Zhu, Timothy R. Lezon, Albert Gough, Andrew M. Stern, Adrian V. Lee, Fiona Ginty, Brion Sarachan, D. Lansing Taylor, S. Chakra Chennubhotla Tags: Focus on Computer Resources Source Type: research

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer
Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) da...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Debra M. Krupke, Dale A. Begley, John P. Sundberg, Joel E. Richardson, Steven B. Neuhauser, Carol J. Bult Tags: Focus on Computer Resources Source Type: research

PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tum...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Terrence F. Meehan, Nathalie Conte, Theodore Goldstein, Giorgio Inghirami, Mark A. Murakami, Sebastian Brabetz, Zhiping Gu, Jeffrey A. Wiser, Patrick Dunn, Dale A. Begley, Debra M. Krupke, Andrea Bertotti, Aleȷandra Bruna, Matthew H. Brush, Annette Tags: Focus on Computer Resources Source Type: research