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Cancer Research

Jeffrey D Robinson, Nathan Dieckmann, Elizabeth Withers, Dena Hassouneh, Charles R Thomas
Audit studies suggest that racial discrimination disadvantages black individuals in educational/professional advancement. We hypothesized that prospective black male doctoral students would experience greater disparity in responses when seeking access to National Cancer Institute (NCI)-funded principal investigators (PI) compared with prospective white males. Primary aim was to explore response and acceptance rates for black versus white men seeking cancer research mentorship. Identical e-mails were sent to 1,028 randomly selected PIs affiliated with 65 NCI-designated cancer centers from "Lamar Washington" (black; n = 515) or "Brad Anderson" (white; n = 513)...
August 17, 2018: Cancer Research
Sandrine Silvente-Poirot, Florence Dalenc, Marc Poirot
Epidemiologic studies are controversial concerning the roles played by cholesterol in cancer risk and development, possibly as it is not cholesterol per se that is pathologic in cancers. Indeed, recent data reveal that the cholesterol metabolism in cancer cells can generate endogenous oncopromoter metabolites at higher levels compared with normal tissues and/or can be deregulated in the production of endogenous oncosuppressor metabolites in an opposite way. These metabolites are oxysterols, which are cholesterol oxygenation products generated by enzymatic and/or autoxidation processes...
August 17, 2018: Cancer Research
Ayesha N Shajahan-Haq, Jeannine M Salamone, Wanda Lucas, Shelley B Brundage, Jamie N Holloway, Sherri M Stahl, Nora E Carbine, Margery London, Naomi Greenwood, Rosa Goyes, Deborah Charles Chisholm, Erin L Price, Roberta Carlin, Susan Winarsky, Kirsten Brecht Baker, Julia Maues
Advocates bring unique and important viewpoints to the cancer research process, ensuring that scientific and medical advances are patient-centered and relevant. In this article, we discuss the benefits of engaging advocates in cancer research and underscore ways in which both the scientific and patient communities can facilitate this mutually beneficial collaboration. We discuss how to establish and nurture successful scientist-advocate relationships throughout the research process. We review opportunities that are available to advocates who want to obtain training in the evaluation of cancer research...
August 17, 2018: Cancer Research
Fernando P Canale, María C Ramello, Nicolás Núñez, Sabrina N Bossio, Eliane Piaggio, Adriana Gruppi, Eva V Acosta Rodríguez, Carolina L Montes
No abstract text is available yet for this article.
August 16, 2018: Cancer Research
Philippe Icard, Ludovic Fournel, Marco Alifano, Hubert Lincet
No abstract text is available yet for this article.
August 16, 2018: Cancer Research
Maria E Mycielska, Edward K Geissler
No abstract text is available yet for this article.
August 16, 2018: Cancer Research
Martin Thelen, Axel Lechner, Kerstin Wennhold, Michael von Bergwelt-Baildon, Hans A Schlößer
No abstract text is available yet for this article.
August 16, 2018: Cancer Research
Yeongseon Byeon, Jeong-Won Lee, Wahn Soo Choi, Ji Eun Won, Ga Hee Kim, Min Gi Kim, Tae In Wi, Jae Myeong Lee, Tae Heung Kang, In Duk Jung, Young-Jae Cho, Hyung Jun Ahn, Byung Cheol Shin, Young Joo Lee, Anil K Sood, Hee Dong Han, Yeong-Min Park
Chemotherapy is commonly used in the treatment of ovarian cancer, yet most ovarian cancers harbor inherent resistance or develop acquired resistance. Therefore, novel therapeutic approaches to overcome chemoresistance are required. In this study, we developed a hyaluronic acid-labeled poly(d,l-lactide-co-glycolide) nanoparticle (HA-PLGA-NP) encapsulating both paclitaxel (PTX) and focal adhesion kinase (FAK) siRNA as a selective delivery system against chemoresistant ovarian cancer. The mean size and zeta potential of the HA-PLGA-NP were 220 nm and -7...
August 16, 2018: Cancer Research
Thibaut Barnoud, Anna Budina-Kolomets, Subhasree Basu, Julia I-Ju Leu, Madeline Good, Che-Pei Kung, Jingjing Liu, Qin Liu, Jessie Villanueva, Rugang Zhang, Donna L George, Maureen E Murphy
The tumor suppressor TP53 is the most frequently mutated gene in human cancer and serves to restrict tumor initiation and progression. Single nucleotide polymorphisms (SNPs) in TP53 and p53 pathway genes can have a marked impact on p53 tumor suppressor function, and some have been associated with increased cancer risk and impaired response to therapy. Approximately 6% of Africans and 1% of African-Americans express a p53 allele with a serine instead of proline at position 47 (Pro47Ser). This SNP impairs p53-mediated apoptosis in response to radiation and genotoxic agents and is associated with increased cancer risk in humans and in a mouse model...
August 16, 2018: Cancer Research
Michal R Tomaszewski, Marcel Gehrung, James Joseph, Isabel Quiros Gonzalez, Jonathan A Disselhorst, Sarah E Bohndiek
Measuring the functional status of tumour vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatio-temporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that overcomes these challenges. By acquiring data at multiple wavelengths, OT can interrogate haemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents...
August 16, 2018: Cancer Research
Thomas F Eleveld, Linda Schild, Jan Koster, Danny A Zwijnenburg, Lindy K Alles, Marli E Ebus, Richard Volckmann, Godelieve A M Tytgat, Peter van Sluis, Rogier Versteeg, Jan J Molenaar
Mutations affecting the RAS-MAPK pathway frequently occur in relapsed neuroblastoma tumors, which suggests that activation of this pathway is associated with a more aggressive phenotype. To explore this hypothesis, we generated several model systems to define a neuroblastoma RAS-MAPK pathway signature. Activation of this pathway in primary tumors indeed correlated with poor survival and was associated with known activating mutations in ALK and other RAS-MAPK pathway genes. Integrative analysis showed that mutations in PHOX2B, CIC, and DMD were also associated with an activated RAS-MAPK pathway...
August 16, 2018: Cancer Research
Sjors M Kas, Julian de Ruiter, Eva Schut, Lorenzo Bombardelli, Ellen Wientjens, Anne Paulien Drenth, Renske de Korte-Grimmerink, Sunny Mahakena, Chris Phillips, Paul D Smith, Sjoerd Klarenbeek, Koen van de Wetering, Anton Berns, Lodewyk F A Wessels, Jos Jonkers, Koen Schipper
In human cancers, fibroblast growth factor receptor (FGFR) signaling is frequently hyperactivated by deregulation of FGF ligands or by activating mutations in the FGFR receptors such as gene amplifications, point mutations and gene fusions. As such, FGFR inhibitors are considered an attractive therapeutic strategy for patients with mutations in FGFR family members. We previously identified Fgfr2 as a key driver of invasive lobular carcinoma (ILC) in an in vivo insertional mutagenesis screen using the Sleeping Beauty (SB) transposon system...
August 16, 2018: Cancer Research
Heather M Gibson, Brooke N McKnight, Agnes Malysa, Gregory Dyson, Wendy Wiesend, Claire E McCarthy, Joyce Reyes, Wei-Zen Wei, Nerissa T Viola-Villegas
Interferon-gamma (IFN-gamma) is an attractive target for imaging active anti-tumor immunity due to its function in the T cell signaling axis. Here we test an IFN-gamma immuno-positron emission tomography (immunoPET) probe for its capacity to identify adaptive immunotherapy (ITx) response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse mammary tumors. IFN-gamma immunoPET detected elevated cytokine levels in situ post-vaccination, which inversely correlated with tumor growth rate, an indicator of response to therapy...
August 16, 2018: Cancer Research
David Dingli, Mi-Yeon Jung, Chetan P Offord, Matthew K Ennis, Iris Kemler, Claudia Neuhauser
The use of replication-competent viruses as oncolytic agents is rapidly expanding, with several oncolytic viruses approved for cancer therapy. As responses to therapy are highly variable, understanding the dynamics of therapy is critical for optimal application of virotherapy in practice. Although mathematical models have been developed to understand the dynamics of tumor virotherapy, a scarcity of in vivo data has made difficult parametrization of these models. To tackle this problem, we studied the in vitro and in vivo spread of two oncolytic measles viruses that induce expression of the sodium iodide symporter (NIS) in cells...
August 16, 2018: Cancer Research
Claudia Capparelli, Timothy J Purwin, Shea A Heilman, Inna Chervoneva, Peter A McCue, Adam C Berger, Michael A Davies, Jeffrey E Gershenwald, Clemens Krepler, Andrew E Aplin
MEK-ERK1/2 signaling is elevated in melanomas that are wild-type for both BRAF and NRAS (WT/WT), but patients are insensitive to MEK inhibitors. Stromal-derived growth factors may mediate resistance to targeted inhibitors, and optimizing the use of targeted inhibitors for WT/WT melanoma patients is a clinical unmet need. Here, we studied adaptive responses to MEK inhibition in WT/WT cutaneous melanoma. TCGA dataset and tumor microarray studies of WT/WT melanomas showed that high levels of neuregulin-1 (NRG1) were associated with stromal content and ErbB3 signaling...
August 16, 2018: Cancer Research
Kaustubh Datta, Sohini Roy, Arup K Bag, Samikshan Dutta, Navatha Shree Polavaram, Ridwan Islam, Samuel Schellenburg, Jasjit K Banwait, Chittibabu Guda, Sophia Ran, Michael A Hollingsworth, Rakesh K Singh, James E Talmadge, Michael H Muders, Surinder K Batra
Tumor-associated macrophages (TAM) are causally associated with tumorigenesis as well as regulation of anti-tumor immune responses and have emerged as potential immunotherapeutic targets. Recent evidence suggests TAM phagocytose apoptotic tumor cells within the tumor microenvironment (TME) through efferocytosis in an immunologically silent manner, thus maintaining an immunosuppressed microenvironment. The signal transduction pathways coupling efferocytosis and immunosuppression are not well known. Neuropilin-2 (NRP2) is member of the membrane-associated neuropilin family and has been reported in different immune cells but is poorly characterized...
August 15, 2018: Cancer Research
Carlos W Wanderley, David F Colon, Joao Paulo Mesquita Luiz, Francisco F Oliveira, Paula R Viacava, Caio A Leite, Janaina A Pereira, Camila M Silva, Cassia R Silva, Rangel L Silva, Cesar A Speck-Hernandez, Jose M Mota, Jose C Alves-Filho, Roberto C Lima-Júnior, Thiago M Cunha, Fernando Q Cunha
Paclitaxel (PCX) is an antineoplastic agent widely used to treat several solid tumor types. The primary mechanism of action of PCX is based on microtubule stabilization inducing cell cycle arrest. Here, we use several tumor models to show that PCX not only induces tumor cell cycle arrest, but also promotes antitumor immunity. In vitro, PCX reprogrammed M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. PCX also modulated the tumor-associated macrophages (TAMs) profile in mouse models of breast and melanoma tumors; gene expression analysis showed that PCX altered the M2-like signature of TAMs toward an M1-like profile...
August 13, 2018: Cancer Research
Antoun Al Absi, Hannah Wurzer, Coralie L Guerin, Céline Hoffmann, Flora Moreau, Xianqing Mao, Joshua Brown-Clay, Rémi Petrolli, Carla Pou Casellas, Monika Dieterle, Jean Paul Thiery, Salem Chouaib, Guy Berchem, Bassam Janji, Clement Thomas
Elucidation of the underlying molecular mechanisms of immune evasion in cancer is critical for the development of immunotherapies aimed to restore and stimulate effective antitumor immunity. Here we evaluate the role of the actin cytoskeleton in breast cancer cell resistance to cytotoxic NK cells. A significant fraction of breast cancer cells responded to NK cell attack via a surprisingly rapid and massive accumulation of F-actin near the immunological synapse, a process we termed 'actin response'. Live cell imaging provided direct evidence that the actin response is associated with tumor cell resistance to NK cell-mediated cell death...
August 13, 2018: Cancer Research
Kristianne M Oristian, Lisa E S Crose, Nina Kuprasertkul, Rex C Bentley, Yi-Tzu Lin, Nerissa Williams, David G Kirsch, Corinne M Linardic
A hallmark of fusion-positive alveolar rhabdomyosarcoma (aRMS) is the presence of a chromosomal translocation encoding the PAX3-FOXO1 fusion oncogene. Primary cell-based modeling experiments have shown that PAX3-FOXO1 is necessary, but not sufficient for aRMS tumorigenesis, indicating additional molecular alterations are required to initiate and sustain tumor growth. Previously we showed that PAX3-FOXO1-positive aRMS is promoted by dysregulated Hippo pathway signaling, as demonstrated by increased YAP1 expression and decreased MST activity...
August 9, 2018: Cancer Research
Bhavna Murali, Qihao Ren, Xianmin Luo, Douglas V Faget, Chun Wang, Radia M Johnson, Tina Gruosso, Kevin C Flanagan, Yujie Fu, Kathleen M Leahy, Elise Alspach, Xinming Su, Michael H Ross, Barry Burnette, Katherine N Weilbaecher, Morag Park, Gabriel Mbalaviele, Joseph Monahan, Sheila A Stewart
The role of the stromal compartment in tumor progression is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKα is frequently expressed in tumor cells and surrounding stromal cells, and its expression levels correlate with poor prognosis. This observation led us to investigate whether inhibition of p38MAPKα could reduce breast cancer metastases in a clinically relevant model. Orally administered, small-molecule inhibitors of p38MAPKα or its downstream kinase MK2, each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs...
August 9, 2018: Cancer Research
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