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Neoplasia: An International Journal for Oncology Research

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https://www.readbyqxmd.com/read/28092823/ph-lactate-and-hypoxia-reciprocity-in-regulating-high-affinity-monocarboxylate-transporter-expression-in-glioblastoma
#1
James P Caruso, Brandon J Koch, Philip D Benson, Elsa Varughese, Michael D Monterey, Amy E Lee, Ajal M Dave, Sam Kiousis, Andrew E Sloan, Saroj P Mathupala
Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs) to prevent "self-poisoning." One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28092822/combination-of-everolimus-with-sorafenib-for-solid-renal-tumors-in-tsc2-mice-is-superior-to-everolimus-alone
#2
Jian Yang, Paulina A Samsel, Kalin Narov, Ashley Jones, Daniel Gallacher, John Gallacher, Julian R Sampson, Ming Hong Shen
Tuberous sclerosis (TSC) is an inherited tumor syndrome caused by mutations in TSC1 or TSC2 that lead to aberrant activation of mTOR and development of tumors in multiple organs including the kidneys. The mTOR inhibitors rapamycin and everolimus (rapalogs) have demonstrated clinical efficacy in treating TSC-associated tumors including renal angiomyolipomas. However, tumor responses are usually only partial, and regrowth occurs after drug withdrawal. TSC-associated tumors are highly vascular, and TSC patients with renal angiomyolipomas have elevated levels of circulating vascular endothelial growth factor (VEGF) A and VEGFD...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28088688/randomized-phase-iii-study-to-assess-efficacy-and-safety-of-adjuvant-capox-with-or-without-bevacizumab-in-patients-after-resection-of-colorectal-liver-metastases-hepatica-study
#3
Nikol Snoeren, Richard van Hillegersberg, Sander B Schouten, Andre M Bergman, Erikv van Werkhoven, Otilia Dalesio, Rob A E M Tollenaar, Henk M Verheul, Joost van der Sijp, Inne H M Borel Rinkes, E E Voest
Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recurrence after resection of colorectal liver metastases (CRLMs), presumably caused by VEGF-mediated outgrowth of micrometastases, might decrease when VEGF is inhibited. This study examines the efficacy and safety of adding bevacizumab to an adjuvant regimen of CAPOX in patients undergoing radical resection for their CRLMs. Patients with resected CRLMs were randomized after surgery to receive CAPOX and bevacizumab (arm A) or CAPOX alone (arm B) as adjuvant treatment...
January 12, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28088687/whole-genome-dna-methylation-profiling-identifies-epigenetic-signatures-of-uterine-carcinosarcoma
#4
Jing Li, Xiaoyun Xing, Daofeng Li, Bo Zhang, David G Mutch, Ian S Hagemann, Ting Wang
Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma...
January 12, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28063307/sharpin-facilitates-p53-degradation-in-breast-cancer-cells
#5
Huijie Yang, Sifan Yu, Weilong Wang, Xin Li, Yingxiang Hou, Zhenhua Liu, Yuanyuan Shi, Kun Mu, Gang Niu, Juntao Xu, Hui Wang, Jian Zhu, Ting Zhuang
The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines...
January 4, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28038320/pan-cancer-analysis-links-park2-to-bcl-xl-dependent-control-of-apoptosis
#6
Yongxing Gong, Steven E Schumacher, Wei H Wu, Fanying Tang, Rameen Beroukhim, Timothy A Chan
Mutation of the PARK2 gene can promote both Parkinson's Disease and cancer, yet the underlying mechanisms of how PARK2 controls cellular physiology is incompletely understood. Here, we show that the PARK2 tumor suppressor controls the apoptotic regulator BCL-XL and modulates programmed cell death. Analysis of approximately 10,000 tumor genomes uncovers a striking pattern of mutual exclusivity between PARK2 genetic loss and amplification of BCL2L1, implicating these genes in a common pathway. PARK2 directly binds to and ubiquitinates BCL-XL...
December 27, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28038319/recruitment-of-tiam1-to-semaphorin-4d-activates-rac-and-enhances-proliferation-invasion-and-metastasis-in-oral-squamous-cell-carcinoma
#7
Hua Zhou, Maricel G Kann, Emily K Mallory, Ying-Hua Yang, Amr Bugshan, Nada O Binmadi, John R Basile
The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth...
December 27, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28013056/matrix-metalloproteinase-14-promotes-lung-cancer-by-cleavage-of-heparin-binding-egf-like-growth-factor
#8
Marcin Stawowczyk, Max D Wellenstein, Sharrell B Lee, Shira Yomtoubian, Anna Durrans, Hyejin Choi, Navneet Narula, Nasser K Altorki, Dingcheng Gao, Vivek Mittal
Molecularly targeted therapies benefit approximately 15-20% of non-small cell lung cancer (NSCLC) patients carrying specific drug-sensitive mutations. Thus, there is a clinically unmet need for the identification of novel targets for drug development. Here, we performed RNA-deep sequencing to identify altered gene expression between malignant and non-malignant lung tissue. Matrix Metalloproteinase 14 (MMP14), a membrane-bound proteinase, was significantly up-regulated in the tumor epithelial cells and intratumoral myeloid compartments in both mouse and human NSCLC...
December 22, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27988457/in-vitro-and-in-vivo-activity-of-lucitanib-in-fgfr1-2-amplified-or-mutated-cancer-models
#9
Federica Guffanti, Rosaria Chilà, Ezia Bello, Massimo Zucchetti, Monique Zangarini, Laura Ceriani, Mariella Ferrari, Monica Lupi, Anne Jacquet-Bescond, Mike F Burbridge, Marie-Jeanne Pierrat, Giovanna Damia
The fibroblast growth factor receptor (FGFR) pathway has been implicated both as an escape mechanism from anti-angiogenic therapy and as a driver oncogene in different tumor types. Lucitanib is a small molecule inhibitor of vascular endothelial growth factor (VEGF) receptors 1 to 3 (VEGFR1 to 3), platelet derived growth factor α/β (PDGFRα/β) and FGFR1-3 tyrosine kinases and has demonstrated activity in a phase I/II clinical study, with objective RECIST responses in breast cancer patients with FGFR1 or FGF3/4/19 gene amplification, as well as in patients anticipated to benefit from anti-angiogenic agents...
December 15, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27987438/unsupervised-analysis-of-array-comparative-genomic-hybridization-data-from-early-onset-colorectal-cancer-reveals-equivalence-with-molecular-classification-and-phenotypes
#10
María Arriba, Juan L García, Daniel Rueda, Jessica Pérez, Lorena Brandariz, Oana A Nutu, Laura Alonso, Yolanda Rodríguez, Miguel Urioste, Rogelio González-Sarmiento, José Perea
AIM: To investigate whether chromosomal instability (CIN) is associated with tumor phenotypes and/or with global genomic status based on MSI (microsatellite instability) and CIMP (CpG island methylator phenotype) in early-onset colorectal cancer (EOCRC). METHODS: Taking as a starting point our previous work in which tumors from 60 EOCRC cases (≤45 years at the time of diagnosis) were analyzed by array comparative genomic hybridization (aCGH), in the present study we performed an unsupervised hierarchical clustering analysis of those aCGH data in order to unveil possible associations between the CIN profile and the clinical features of the tumors...
December 14, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27987437/theranostic-approach-for-metastatic-pigmented-melanoma-using-icf15002-a-multimodal-radiotracer-for-both-pet-imaging-and-targeted-radionuclide-therapy
#11
Latifa Rbah-Vidal, Aurélien Vidal, Emilie M F Billaud, Sophie Besse, Isabelle Ranchon-Cole, Florence Mishellany, Yann Perrot, Lydia Maigne, Nicole Moins, Jean-Luc Guerquin-Kern, Françoise Degoul, Jean-Michel Chezal, Philippe Auzeloux, Elisabeth Miot-Noirault
PURPOSE: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound. METHODS: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET) imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT)...
December 14, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27940248/integrin-targeted-hybrid-fluorescence-molecular-tomography-x-ray-computed-tomography-for-imaging-tumor-progression-and-early-response-in-non-small-cell-lung-cancer
#12
Xiaopeng Ma, Valerie Phi Van, Melanie A Kimm, Jaya Prakash, Horst Kessler, Katja Kosanke, Annette Feuchtinger, Michaela Aichler, Aayush Gupta, Ernst J Rummeny, Michel Eisenblätter, Jens Siveke, Axel K Walch, Rickmer Braren, Vasilis Ntziachristos, Moritz Wildgruber
Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC) model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF) probe...
December 7, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27940247/sdf-1-blockade-enhances-anti-vegf-therapy-of-glioblastoma-and-can-be-monitored-by-mri
#13
Lei Deng, Jason H Stafford, Shie-Chau Liu, Sophia B Chernikova, Milton Merchant, Lawrence Recht, J Martin Brown
Despite the approval of antiangiogenic therapy for glioblastoma multiforme (GBM) patients, survival benefits are still limited. One of the resistance mechanisms for antiangiogenic therapy is the induction of hypoxia and subsequent recruitment of macrophages by stromal-derived factor (SDF)-1α (CXCL-12). In this study, we tested whether olaptesed pegol (OLA-PEG, NOX-A12), a novel SDF-1α inhibitor, could reverse the recruitment of macrophages and potentiate the antitumor effect of anti-vascular endothelial growth factor (VEGF) therapy...
December 7, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27973325/upregulation-of-glucose-regulated-protein-78-in-metastatic-cancer-cells-is-necessary-for-lung-metastasis-progression
#14
Michael M Lizardo, James J Morrow, Tyler E Miller, Ellen S Hong, Ling Ren, Arnulfo Mendoza, Charles H Halsey, Peter C Scacheri, Lee J Helman, Chand Khanna
Metastasis is the cause of more than 90% of all cancer deaths. Despite this fact, most anticancer therapeutics currently in clinical use have limited efficacy in treating established metastases. Here, we identify the endoplasmic reticulum chaperone protein, glucose-regulated protein 78 (GRP78), as a metastatic dependency in several highly metastatic cancer cell models. We find that GRP78 is consistently upregulated when highly metastatic cancer cells colonize the lung microenvironment and that mitigation of GRP78 upregulation via short hairpin RNA or treatment with the small molecule IT-139, which is currently under clinical investigation for the treatment of primary tumors, inhibits metastatic growth in the lung microenvironment...
October 28, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27978998/corrigendum-to-noninvasive-multimodality-imaging-of-the-tumor-microenvironment-registered-dynamic-magnetic-resonance-imaging-and-positron-emission-tomography-studies-of-a-preclinical-tumor-model-of-tumor-hypoxia-neoplasia-11-2009-247-259
#15
HyungJoon Cho, Ellen Ackerstaff, Sean Carlin, Mihaela E Lupu, Ya Wang, Asif Rizwan, Joseph O'Donoghue, C Clifton Ling, John L Humm, Pat B Zanzonico, Jason A Koutcher
No abstract text is available yet for this article.
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27978997/corrigendum-to-kdm4c-a-h3k9me3-histone-demethylase-is-involved-in-the-maintenance-of-human-escc-initiating-cells-by-epigenetically-enhancing-sox2-expression-neoplasia-18-2016-594-609
#16
Xiang Yuan, Jinyu Kong, Zhikun Ma, Na Li, Ruinuo Jia, Yiwen Liu, Fuyou Zhou, Qimin Zhan, Gang Liu, Shegan Gao
No abstract text is available yet for this article.
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27978996/corrigendum-to-a-potent-derivative-of-indolizino-6-7-b-indole-for-treatment-of-human-non-small-cell-lung-cancer-cells-neoplasia-18-2016-199-212
#17
Chi-Wei Chen, Ming-Hsi Wu, Yi-Fan Chen, Tsai-Yi Yen, Yi-Wen Lin, Shu-Hsin Chao, Satishkumar Tala, Tung-Hu Tsai, Tsann-Long Su, Te-Chang Lee
No abstract text is available yet for this article.
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27978995/precision-medicine-with-tgf-%C3%AE-inhibition-using-tumor-explants-comment-on-patient-specific-screening-using-high-grade-glioma-explants-to-determine-potential-radiosensitization-by-a-tgf-%C3%AE-small-molecule-inhibitor-by-n-sumru-bayin-et-al
#18
Haidong Huang, Jennifer S Yu
In a new report, Bayin et al. described an ex vivo explant model to test the patient-specific response to transforming growth factor-β inhibition in high-grade gliomas.
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27978994/patient-specific-screening-using-high-grade-glioma-explants-to-determine-potential-radiosensitization-by-a-tgf-%C3%AE-small-molecule-inhibitor
#19
N Sumru Bayin, Lin Ma, Cheddhi Thomas, Rabaa Baitalmal, Akhila Sure, Kush Fansiwala, Mark Bustoros, John G Golfinos, Donato Pacione, Matija Snuderl, David Zagzag, Mary Helen Barcellos-Hoff, Dimitris Placantonakis
High-grade glioma (HGG), a deadly primary brain malignancy, manifests radioresistance mediated by cell-intrinsic and microenvironmental mechanisms. High levels of the cytokine transforming growth factor-β (TGF-β) in HGG promote radioresistance by enforcing an effective DNA damage response and supporting glioma stem cell self-renewal. Our analysis of HGG TCGA data and immunohistochemical staining of phosphorylated Smad2, which is the main transducer of canonical TGF-β signaling, indicated variable levels of TGF-β pathway activation across HGG tumors...
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27889647/activation-of-wnt-%C3%AE-catenin-signaling-enhances-pancreatic-cancer-development-and-the-malignant-potential-via-up-regulation-of-cyr61
#20
Makoto Sano, David R Driscoll, Wilfredo E DeJesus-Monge, Brian Quattrochi, Victoria A Appleman, Jianhong Ou, Lihua Julie Zhu, Nao Yoshida, Shintaro Yamazaki, Tadatoshi Takayama, Masahiko Sugitani, Norimichi Nemoto, David S Klimstra, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras(G12D), Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin(S37A) and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development...
December 2016: Neoplasia: An International Journal for Oncology Research
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