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  • In Vitro Patients Derived Glioma Culture Model: Identification of Aggressive, Drug Resistant Phenotype Among Low-Grade Gliomas
    bioRxiv. Cancer Biol. Pub Date : 2020-06-05
    Syed Sultan Beevi; Vinod Kumar Verma; Manas Panigrahi; Aishwarya Bhale; Sailaja Madigubba; Radhika Chowdary; Radhika Korabathina; Sukrutha Gopal Reddy

    Background: Low-grade gliomas are mostly played down as less fatal malignancy despite the fact that most of them eventually progress to high grade thereby leading to death. In vitro glioma cultures have been emerged as a standard model to get insight into phenotypic transformation, drug response and tumor relapse. In this study, attempt was made to establish comprehensive patient-specific short-term

    更新日期:2020-06-05
  • Use of signals of positive and negative selection to distinguish cancer genes and passenger genes
    bioRxiv. Cancer Biol. Pub Date : 2020-06-05
    Laszlo Banyai; Maria Trexler; Krisztina Kerekes; Orsolya Csuka; Laszlo Patthy

    Abstract Background A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most of the approaches aimed to achieve this goal focused on genes that are positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. Results

    更新日期:2020-06-05
  • Sensitivity of radio-photoluminescence glass dosimeters to accumulated doses
    bioRxiv. Cancer Biol. Pub Date : 2020-06-05
    Dong Wook Kim; Jiwon Sung; Jaeman Son; Han-Back Shin; Min-Joo Kim; Yu-Yun Noh; Hojae Kim; Min Cheol Han; Jihun Kim; Su Chul Han; Kyung Hwan Chang; Hojin Kim; Kwangwoo Park; Myonggeun Yoon; Jinsung Kim; Dongoh Shin

    Background: This study investigated the effect of accumulated doses on radio-photoluminescence glass dosimeters (RPLGDs) from measurements involving mega-voltage photons. Methods: Forty-five commercially available RPLGDs were irradiated to estimate their dose responses. Photon beams of 6, 10, and 15 MV were irradiated onto the RPLGDs inside a phantom, which were divided into five groups with different

    更新日期:2020-06-05
  • Skin Lesions Classification Using Deep Learning Based on Dilated Convolution
    bioRxiv. Cancer Biol. Pub Date : 2020-06-05
    Md. Aminur Rab Ratul; M. Hamed Mozaffari; Dr. WonSook Lee; Dr. Enea Parimbelli

    The prediction of skin lesions is a challenging task even for experienced dermatologists due to a little contrast between surrounding skin and lesions, the visual resemblance between skin lesions, fuddled lesion border, etc. An automated computer-aided detection system with given images can help clinicians to prognosis malignant skin lesions at the earliest time. Recent progress in deep learning includes

    更新日期:2020-06-05
  • Towards a consensus microRNA signature of primary and metastatic colorectal cancer
    bioRxiv. Cancer Biol. Pub Date : 2020-06-05
    Bastian Fromm; Eirik Hoye; Paul Heinrich Michael Bottger; Diana Domanska; Annette Torgunrud Kristensen; Christin Lund-Andersen; Torveig Weum Abrahamsen; Asmund Avdem Fretland; Vegar Johansen Dagenborg; Susanne Lorenz; Bjorn Edwin; Eivind Hovig; Kjersti Flatmark

    Background: Although microRNAs (miRNAs) are involved in all hallmarks of cancer, miRNA dysregulation in the metastatic process remains poorly understood. We investigated the role of miRNAs in metastatic evolution of colorectal cancer (CRC) by analyzing smallRNA-seq datasets from primary CRC, metastatic locations (liver, lung and peritoneum), and corresponding adjacent tissues. Addressing main challenges

    更新日期:2020-06-05
  • Fructose fuels tumor growth through the polyol pathway and GLUT 8 transporter
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    BING HAN; Lu Wang; Meilin Wei; Cynthia Rajani; Haining Yang; Guoxiang Xie; wei jia

    Fructose metabolism is increasingly recognized as a preferred energy source for cancer cell proliferation. However, dietary fructose rarely enters the bloodstream, and its fasting blood levels are much lower (~0.005 mM) than glucose (~5.5 mM) under normal physiological conditions. Therefore, it remains unclear where fructose is derived from and how cancer cells acquire a sufficient amount of fructose

    更新日期:2020-06-04
  • SLX4IP-mediated telomere maintenance is essential for androgen receptor-independent castration-resistant prostate cancer
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Tawna L Mangosh; Wisam N Awadallah; Magdalena M Grabowska; Derek J Taylor

    In advanced prostate cancer, resistance to androgen deprivation therapy is achieved through numerous mechanisms, including loss of the androgen receptor (AR) allowing for AR-independent growth. Therapeutic options are limited for AR-independent castration-resistant prostate cancer, and defining mechanisms critical for its survival is of utmost importance for targeting this lethal disease. Our studies

    更新日期:2020-06-04
  • In silico saturation mutagenesis of cancer genes
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Ferran Muinos; Francisco Martinez-Jimenez; Oriol Pich; Abel Gonzalez-Perez; Nuria Lopez-Bigas

    Extensive bioinformatics analysis of these datasets of tumor somatic mutations data have revealed the presence of some 500-600 cancer driver genes. The identification of all potential driver mutations affecting cancer genes is essential to implement precision cancer medicine and to understand the interplay of mutation probability and selection in tumor development. Here, we present an in silico saturation

    更新日期:2020-06-04
  • Precision combination therapies from recurrent oncogenic co-alterations
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Xubin Li; Elisabeth Dowling; Gonghong Yan; Behnaz Bozorgui; Parisa Imanirad; Jacob H Elnaggar; Augustin Luna; Chris Sander; Anil Korkut

    Cancer cells rely on co-activation of oncogenic processes that are driven by co-occurring molecular aberrations. Combination therapies that target co-activated oncogenic processes can induce stronger and more durable responses compared to mono-therapies. Here, we developed REFLECT (REcurrent Features Leveraged for Combination Therapies) to match precision combination therapies to co-alteration signatures

    更新日期:2020-06-04
  • Selective Vulnerability of Senescent Glioblastoma Cells to Bcl-XL Inhibition
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Masum Rahman; Ian Edward Olson; Moustafa Mansour; Lucas P. Carlstrom; Rujapope Sutiwisesak; Rehan Saber; Karishma Rajani; Arthur E Warrington; Adam Howard; Mark Schroeder; Sisi Chen; Paul A. Decker; Yi Zhu; Ian F. Parney; Sandeep Burma; Desmond Brown; Moses Rodriguez; Jann N. Sarkaria; James Kirkland; Terry Burns

    Despite decades of research and numerous basic science advances, there have only marginal gains in improving glioblastoma multiforme survival. Therefore, new ideas and approaches for treating this aggressive disease are essential to drive progress forward. Conventional therapies, such as radiation and Temozolomide (TMZ), function to cause oxidative stress and DNA damage yielding a senescent-like state

    更新日期:2020-06-04
  • The therapeutic effects of intratumoral injection of IL12IL2GMCSF fusion protein on canine tumors
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Xiaobo Du; Bin Zhang; Fan Hu; Chuantao Xie; Haiyan Tian; Qiang Gu; Haohan Gong; Xiaoguang Bai; Jinyu Zhang

    Regulating the immune system through tumor immunotherapy to defeat tumors is currently one of the most popular methods of tumor treatment. We previously found that the combinations of IL12, IL2 and GMCSF has superior antitumor activities. In this study, IL12IL2GMCSF fusion protein was produced from 293 cells transduced by expression lentiviral vector. IL12IL2GMCSF fusion protein was injected into canine

    更新日期:2020-06-04
  • UBR-Box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    kumar Saurabh; Parag Shah; Mark Doll; Leah J Siskind; Levi J Beverly

    Background: N-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer. Methods: We determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples. Using immunoprecipitation followed by mass spectrometry

    更新日期:2020-06-04
  • Impact of the radiated brain microenvironment on a panel of human patient-derived xenografts.
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Jibo Zhang; Ian E. Olson; Lucas P. Carlstrom; Masum Rahman; Karishma Rajani; Kshama Gupta; Libo Liu; Zhi Tang; Eliot F. Sananikone; Anqin Dong; Arthur E. Warrington; Moses Rodriguez; Jincao Chen; Mark A. Schroeder; Samar Ikram; Jann N. Sarkaria; Sandeep Burma; Terry C. Burns

    Objective: Radiotherapy, combined with surgical resection and chemotherapy, remains a first-line treatment for infiltrative gliomas. However, these tumor are not surgically curable, and often recur, even within the prior radiation field, and may demonstrate a more aggressive phenotype. We recently demonstrated that the radiated brain tumor microenvironment promotes tumor aggressiveness in an orthotopic

    更新日期:2020-06-04
  • Patient Similarity Network of Multiple Myeloma Identifies Patient Sub-groups with Distinct Genetic and Clinical Features
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Sherry Bhalla; David T Melnekoff; Jonathan Keats; Kenan Onel; Deepu Madduri; Joshua Richter; Shambavi Richard; Ajai Chari; Hearn Jay Cho; Joel T Dudley; Sundar Jagannath; Alessandro Lagana; Samir Parekh

    The remarkable genetic heterogeneity of Multiple Myeloma (MM) poses a significant challenge for proper prognostication and clinical management of patients. Accurate dissection of the genetic and molecular landscape of the disease and the robust identification of homogeneous classes of patients are essential steps to reliable risk stratification and the development of novel precision medicine strategies

    更新日期:2020-06-04
  • Kinobead Profiling Reveals Reprogramming of B-cell Receptor Signaling in Response to Therapy Within Primary Chronic Lymphocytic Leukemia Cells.
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Adam J Linley; Laura Karydis; Anil Mondru; Annalisa D'Avola; Silvia Cicconi; Rebecca Griffin; Francesco Forconi; Andrew R Pettitt; Nagesh Kalakonda; Andy Rawstron; Peter Hillmen; Andrew J Steele; David J MacEwan; Graham Packham; Ian Prior; Joseph Slupsky

    Signaling via the B-cell receptor (BCR) is critical for driving CLL pathobiology, promoting both malignant cell survival and disease progression. However, understanding of this pathway is limited, particularly in relation to potential changes in response to therapy. Here, we describe a kinobead-based protocol, used in conjunction with mass-spectrometry to study surface-IgM signaling in primary CLL

    更新日期:2020-06-04
  • Mutational processes impact the evolution of anti-EGFR antibody resistance in colorectal cancer
    bioRxiv. Cancer Biol. Pub Date : 2020-06-04
    Andrew Woolston; Louise J Barber; Beatrice Griffiths; Nik Matthews; Sheela Rao; David Watkins; Ian Chau; Naureen Starling; David Cunningham; Marco Gerlinger

    Background: Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRC) but acquired resistance invariably evolves. Biomarkers that can be assessed prior to treatment to predict the time to resistance and the genetic resistance mechanisms that will evolve have not been identified. Distinct mutational signatures have been described in cancer and differences

    更新日期:2020-06-04
  • Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells
    bioRxiv. Cancer Biol. Pub Date : 2020-06-03
    Zimple Kurlawala; Kumar Saurabh; Rain Dunaway; Parag Shah; Leah J Siskind; Levi J Beverly

    Ubiquilin proteins (UBQLNs) are involved in diverse cellular processes like ERAD (endoplasmic reticulum associated degradation), autophagy, apoptosis and epithelial to mesenchymal transition. UBQLNs interact with a variety of substrates, including cell surface receptors, transcription factor regulators, proteasomal machinery proteins, and transmembrane proteins. Additionally, previous work from our

    更新日期:2020-06-03
  • CRTC1-MAML2 Establishes a PGC1α-IGF1 Circuit that Confers Vulnerability to PPARγ Inhibition
    bioRxiv. Cancer Biol. Pub Date : 2020-06-03
    Adele M Musicant; Kshitij Parag-Sharma; Weida Gong; Monideepa Sengupta; Arindam Chatterjee; Erin C Henry; Yi-Hsuan Tsai; Michele Hayward; Siddharth Sheth; Renee Betancourt; Trevor Hackman; Ricardo J Padilla; Joel S Parker; Jimena Giudice; Colin A Flaveny; David N Hayes; Antonio L. Amelio

    Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by the transcriptional co-activator fusion CRTC1-MAML2. The mechanisms by which the chimeric CRTC1-MAML2 oncoprotein rewires gene expression programs that promote tumorigenesis remain poorly understood. Here, we show that CRTC1-MAML2 induces transcriptional activation of the non-canonical PGC-1 α splice

    更新日期:2020-06-03
  • Immunotherapy with immunocytokines and PD-1 blockade enhances the anticancer activity of small molecule-drug conjugates targeting carbonic anhydrase IX
    bioRxiv. Cancer Biol. Pub Date : 2020-06-03
    Jacopo Millul; Christiane Krudewig; Sheila Dakhel Plaza; Emanuele Puca; Alessandra Villa; Dario Neri; Samuele Cazzamalli

    Small molecule-drug conjugates (SMDCs) represent an alternative to conventional anti-tumor chemotherapeutic agents, with the potential to improve the therapeutic window of cytotoxic payloads through active delivery at the site of the disease. In this article we de-scribe novel combination therapies consisting of anti-Carbonic Anhydrase IX SMDCs combined with different immunomodulatory products. The

    更新日期:2020-06-03
  • Development and Characterization of Patient-Derived Xenografts from Non-Small Cell Lung Cancer Brain Metastases
    bioRxiv. Cancer Biol. Pub Date : 2020-06-03
    Andrew M Baschnagel; Saakshi Kaushik; Arda Durmaz; Steve Goldstein; Irene M Ong; Lindsey Abel; Paul A Clark; Ticiana Leal; Darya Buehler; Gopal Iyer; Jacob G Scott; Randall J Kimple

    Introduction: NSCLC brain metastasis cell lines and in vivo brain metastasis models are not widely accessible. The purpose of this study was to establish and characterize a direct-from patient-derived xenograft (PDX) model of non-small cell lung cancer (NSCLC) brain metastases. Methods: Surgically obtained tissue was implanted subcutaneously and as orthotopic intracranial implants into immunodeficient

    更新日期:2020-06-03
  • Therapy-induced transdifferentiation promotes glioma growth independent of EGFR signaling
    bioRxiv. Cancer Biol. Pub Date : 2020-06-03
    Hwanhee Oh; Inah Hwang; Lingxiang Wu; Dongqing Cao; Jun Yao; Haoqiang Ying; Jian Yi Li; Yu Yao; Baoli Hu; Qianghu Wang; Hongwu Zheng; Jihye Paik

    Epidermal growth factor receptor (EGFR) is frequently amplified, mutated and overexpressed in malignant gliomas. Yet the EGFR-targeted therapies have thus far produced only marginal clinical response, and the underlying mechanism remains poorly understood. Through analyses of an inducible oncogenic EGFR-driven glioma mouse model system, our current study reveals a small population of glioma cells that

    更新日期:2020-06-03
  • Inhibition of CAMKK2 impairs autophagy and castration-resistant prostate cancer via suppression of AMPK-ULK1 signaling
    bioRxiv. Cancer Biol. Pub Date : 2020-06-03
    Chenchu Lin; Alicia M. Blessing; Thomas L. Pulliam; Yan Shi; Sandi R. Wilkenfeld; Jenny J. Han; Mollianne M. Murray; Alexander H. Pham; Kevin Duong; Sonja N. Brun; Reuben J. Shaw; Michael M. Ittmann; Daniel E. Frigo

    Previous work has suggested androgen receptor (AR) signaling mediates cancer progression in part through the modulation of autophagy. Accordingly, we demonstrate that chloroquine, an inhibitor of autophagy, can inhibit tumor growth in preclinical mouse models of castration-resistant prostate cancer (CRPC). However, clinical trials testing chloroquine derivatives in men with CRPC have yet to yield promising

    更新日期:2020-06-03
  • CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
    bioRxiv. Cancer Biol. Pub Date : 2020-06-03
    Paulino Tallon de Lara; Hector Castanon Cuadrado; Marijne Vermeer; Nicolas Nunez; Karina Silina; Bettina Sobottka; Joaquin Urdinez; Virginia Cecconi; Farkhondeh Movahedian Attar; Stefanie Hiltbrunner; Isabelle Glarner; Holger Moch; Sonia Tugues; Burkhard Becher; Maries van den Broek

    Some breast tumors metastasize aggressively whereas others remain in a state of metastatic dormancy for months or even years. The mechanism governing such metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping, we identified a discrete population of CD39+PD-1+CD8+ T cells present both in primary tumors and in dormant metastasis, which was hardly found in aggressively

    更新日期:2020-06-03
  • Detection of Chemotherapy-Resistant Pancreatic Cancer Using a Glycan Biomarker
    bioRxiv. Cancer Biol. Pub Date : 2020-06-02
    ChongFeng Gao; Luke Wisniewski; Ying Liu; Ben Staal; Ian Beddows; Dennis Plenker; Mohammed Aldakkak; Johnathan Hall; Daniel Barnett; Mirna Kheir Gouda; Peter Allen; Richard Drake; Amer Zureikat; Ying Huang; Douglas Evans; Aatur Singhi; Randall E Brand; David A Tuveson; Susan Tsai; Brian Haab

    Background and Aims: A subset of pancreatic ductal adenocarcinomas (PDACs) is highly resistant to systemic chemotherapy, but no markers are available in clinical settings to identify this subset. We hypothesized that chemotherapy-resistant PDACs express a glycan biomarker called sTRA. Methods. We tested this marker to identify treatment-resistant PDAC in multiple systems: sets of cell lines, organoids

    更新日期:2020-06-02
  • Lineage and Spatial Mapping of Glioblastoma-associated Immunity
    bioRxiv. Cancer Biol. Pub Date : 2020-06-02
    Vidhya Madapusi Ravi; Nicolas Neidert; Paulina Will; Kevin Joseph; Jan Kuekelhaus; Lea Vollmer; Jonathan Goeldner; Simon Behringer; Florian Scherer; Melanie Boerries; Marie Follo; Tobias Weiss; Daniel Delev; Julius Kernbach; Pamela Franco; Nils Schallner; Christian Scheiwe; Maria Stella Carro; Ulrich G Hofmann; Christian Fung; Juergen Beck; Roman Sankowski; Marco Prinz; Oliver Schnell; Dieter Henrik

    The diversity of molecular states and cellular plasticity of immune cells within the glioblastoma (GBM) environment remain poorly investigated. Here, we performed deep transcriptional profiling of lymphoid and myeloid cell populations by scRNA-sequencing, and mapped potential cellular interactions and cytokine responses that lead to the dysfunctional and exhausted phenotype of T cells. We identified

    更新日期:2020-06-02
  • Chemical, physical and biological triggers of Bcl-xL-mediated apoptosis
    bioRxiv. Cancer Biol. Pub Date : 2020-06-02
    Aleksandr Ianevski; Evgeny Kulesskiy; Klara Krpina; Guofeng Lou; Yahyah Aman; Andrii Bugai; Koit Aasumets; Yevhen Akimov; Daria Bulanova; Kiira Gildemann; Albert F Arutyunyan; Olga Yu Susova; Alexei L Zhuze; Ping Ji; Wei Wang; Toril Holien; Marit Bugge; Eva Zusinaite; Valentyn Oksenych; Hilde Lysvand; Joachim Gerhold; Magnar Bjørås; Anders Waage; Pål Johansen; Caroline Heckman; Evandro F Fang; Denis

    The evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected or RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. Here, we show that Bcl-xL-specific agent A-1155463 prematurely kills cells of different origins and the small roundworms (C. elegans), when combined with DNA-damaging agent 4-nitroquinoline-1-oxide (4NQO). The synergistic

    更新日期:2020-06-02
  • Induction of pancreatic neoplasia in the KRAS/TP53 Oncopig: preliminary report
    bioRxiv. Cancer Biol. Pub Date : 2020-06-02
    Neesha Patel; Katie Bailey; Audrey J. Lazenby; Mark A. Carlson

    Introduction: Five-year survival (all patients) from pancreatic cancer (PC) is in the range of 10%, and has not changed substantially in decades. Current murine models may not adequately mimic human PC, and can be inadequate for device development, which all may contribute to the lack of progress in PC survival. We attempted PC induction in transgenic swine (expressing KRAS and TP53 mutants) with the

    更新日期:2020-06-02
  • A novel mechanism of natural killer cell response to anti-CTLA-4 therapy identified by integrative analysis of mouse and human tumors
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Emily F Davis-Marcisak; Allison A. Fitzgerald; Michael D. Kessler; Ludmila Danilova; Elizabeth M. Jaffee; Neeha Zaidi; Louis M. Weiner; Elana J Fertig

    Immune checkpoint-inhibitory antibodies (ICIs) are well-established immunotherapies. Despite this, the impact of ICI therapy on non-T cell intratumoral immune cells is ill-defined, restraining the improvement of ICI efficacy. Preclinical murine models of human disease are infrequently validated in clinical trials, impairing the identification of novel biological factors impacting clinical ICI response

    更新日期:2020-05-31
  • Deletion and overexpression of the scaffolding protein IQGAP1 promotes HCC
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Evan R Delgado; Hanna L Erickson; Junyan Tao; Satdarshan P Monga; Andrew W Duncan; Sayeepriyadarshini Anakk

    IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffolding protein that is overexpressed in a number of cancers, including liver cancer, and is associated with many pro-tumorigenic processes including cell proliferation, motility, and adhesion. IQGAP1 can integrate multiple signaling pathways and could be an effective antitumor target. Therefore, we examined the

    更新日期:2020-05-31
  • SHP2 Inhibition Abrogates Adaptive Resistance to KRASG12C-Inhibition and Remodels the Tumor Microenvironment of KRAS-Mutant Tumors
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Carmine Fedele; Shuai Li; Kai Wen Teng; Connor Foster; David Peng; Hao Ran; Paolo Mita; Mitchell Geer; Takamitsu Hattori; Akiko Koide; Yubao Wang; Kwan Ho Tang; Joshua Leinwand; Wei Wang; Brian Diskin; Jiehui Deng; Ting Chen; Igor Dolgalev; Ugur Ozerdem; George Miller; Shohei Koide; Kwok-Kin Wong; Benjamin G. Neel

    KRAS is the most frequently mutated oncogene in human cancer, and KRAS inhibition has been a longtime therapeutic goal. Recently, inhibitors (G12C-Is) that bind KRASG12C-GDP and react with Cys-12 were developed. Using new affinity reagents to monitor KRASG12C activation and inhibitor engagement, we found that, reflecting its action upstream of SOS1/2, SHP2 inhibitors (SHP2-Is) increased KRAS-GDP occupancy

    更新日期:2020-05-31
  • Metabolic control of tumour extracellular matrix production in cancer-associated fibroblasts
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Emily J Kay; Karla Paterson; David Sumpton; Ekaterina Stepanova; Claudia Boldrini; Juan R Hernandez-Fernaud; Sandeep Dhayade; Enio Gjerga; Robin Shaw; Lisa J Neilson; Grigoris Koulouras; Grace McGregor; Sergio Lilla; Craig Jamieson; Ann Hedley; Radia M Johnson; Morag Park; Crispin Miller; Jurre Kamphorst; Fabrizio Loayza-Puch; Julio Saez-Rodriguez; Karen Blyth; Michele Zagnoni; Sara Zanivan

    The extracellular matrix (ECM) is the central driver of the desmoplastic reaction that fosters cancer aggressiveness. Cancer associated fibroblasts (CAFs) are the major source of ECM in tumours, thus being the optimal target to limit deposition of pro-tumourigenic ECM to oppose cancer. CAFs are metabolically active cells, however, how they support the biosynthetic requirements of producing ECM, and

    更新日期:2020-05-31
  • UDP-Glucose 6-Dehydrogenase Knockout Impairs Migration and Decreases in vivo Metastatic Ability of Breast Cancer Cells
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Shao Thing Teoh; Martin P Ogrodzinski; Sophia Lunt

    Dysregulated metabolism is a hallmark of cancer that supports tumor growth and metastasis. One understudied aspect of cancer metabolism is altered nucleotide sugar biosynthesis, which drives aberrant cell surface glycosylation known to support various aspects of cancer cell behavior including migration and signaling. We examined clinical association of nucleotide sugar pathway gene expression and found

    更新日期:2020-05-31
  • Intra-tumor heterogeneity of Diffuse Large B-cell Lymphoma involves the induction of diversified stroma-tumor interfaces
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Sabina Sangaletti; Fabio Iannelli; Federica Zanardi; Valeria Cancila; Paola Portararo; Laura Botti; Davide Vacca; Claudia Chiodoni; Arianna Di Napoli; Cesare Valenti; Maria Carmela Vegliante; Federica Pisati; Alessandro Gulino; Maurilio Ponzoni; Mario Paolo Colombo; Claudio Tripodo

    Intra-tumor heterogeneity in lymphoid malignancies is articulated around several fundamentals, encompassing selection of genetic subclonal events and epigenetic regulation of transcriptional programs. Clonally-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-intrinsic mesenchymal determinants

    更新日期:2020-05-31
  • Lyn controls chemotaxis and motility of CLL cells via phosphorylation of ROR1.
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Zankruti Dave; Olga Vondálová-Blanářova; Štepan Čada; Pavlína Janovská; Nikodém Zezula; Martin Běhal; Kateřina Hanáková; Sri Ranjani Ganjani; Pavel Krejci; Kristína Gmöryövá; Helena Peschelová; Michal Šmida; Zbyněk Zdráhal; Šarka Pavlová; Jana Kotašková; Šarka Pospíšilová; Vitezslav Bryja

    Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are malignancies characterized by the dependence on B-cell receptor (BCR) signaling and by the high expression of the cell surface receptor ROR1. Both, BCR and ROR1 are therapeutic targets in these diseases and the understanding of their mutual cross talk is thus of direct therapeutic relevance. In this study we analyzed the role of

    更新日期:2020-05-31
  • HSP90 facilitates oncogenic alterations of metabolism in B-cell lymphomas
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    M Nieves Calvo-Vidal; Nahuel Zamponi; Jan Krumsiek; Max A Stockslager; Maria Victoria Revuelta; Jude M Phillip; Rossella Marullo; Nikita Kotlov; Jayeshkumar Patel; Shao Ning Yang; Lucy Yang; Tony Taldone; Catherine Thieblemont; John P Leonard; Peter Martin; Giorgio Inghirami; Gabriela Chiosis; Scott R Manalis; Leandro Cerchietti

    HSP90 is critical for maintenance of the cellular proteostasis. In cancer cells, HSP90 also becomes a nucleating site for the stabilization of multiprotein complexes including signaling pathways and transcription complexes. Here, we described a novel role of HSP90 in the cytosolic compartmentalization of metabolic pathways in proliferating cancer cells. We found that HSP90 assists in the organization

    更新日期:2020-05-31
  • Loss of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    H. Furkan Alkan; Paul Vesely; Hubert Hackl; Johannes Fosselteder; Matthew Vander Heiden; Martin Pichler; Gerald Hoefler; Juliane Bogner-Strauss

    Background: Aspartate biosynthesis and its delivery to the cytosol can be crucial for tumor growth in vivo. However, the impact of aspartate synthesis on metastasis has not been studied. We previously described that loss-of-aspartate glutamate carrier 1 (SLC25A12 or AGC1), an important component of the malate-aspartate shuttle, impairs cytosolic aspartate levels, NAD+/NADH ratio, mitochondrial respiration

    更新日期:2020-05-31
  • Core binding factor leukemia hijacks T-cell prone PU.1 antisense promoter
    bioRxiv. Cancer Biol. Pub Date : 2020-05-31
    Emiel van der Kouwe; Gerwin Heller; Akos Czibere; Lucio H Castilla; Ruud Delwel; Annalisa Di Ruscio; Alexander K Ebralidze; Maurizio Forte; Lukas Kazianka; Christoph Kornauth; Trang Le; Karin Lind; Ines A Monteiro Barbosa; Alexander Pichler; John A Pulikkan; Ann-Sofie Schmolke; Heinz Sill; Wolfgang Sperr; Andreas Spittler; Bon Q Trinh; Peter Valent; Katrina Vanura; Robert S Welner; Johannes Zuber;

    The blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of the hematopoietic master regulator PU.1. PU.1 gene expression is regulated through enhancer-promoter interactions within a topologically associated domain (TAD). PU.1 levels increase during myeloid differentiation while failure to do so results in myeloid leukemia.

    更新日期:2020-05-31
  • Frizzled-7 Identifies Platinum Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Yinu Wang; Guanyuan Zhao; Salvatore Condello; Hao Huang; Horacio Cardenas; Edward Tanner; Jian-Jun Wei; Yanrong Ji; Junjie Li; Yuying Tan; Ramana Davuluri; Ji-Xin Cheng; Daniela Matei

    Defining traits of platinum tolerant cancer cells could expose new treatment vulnerabilities. Here, new markers associated with platinum tolerant cells and tumors were identified by using in vitro and in vivo ovarian cancer (OC) models treated repetitively with carboplatin and validated in human specimens. Platinum-tolerant cells and tumors were found to be enriched in ALDH (+) cells, formed more spheroids

    更新日期:2020-05-30
  • Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during periods of clinical latency
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Melanie Werner-Klein; Ana Grujovic; Christoph Irlbeck; Milan Obradovic; Martin Hoffmann; Huiqin Koerkel-Qu; Xin Lu; Steffie Treitschke; Caecilia Koestler; Catherine Botteron; Kathrin Weidele; Christian Werno; Bernhard Polzer; Stefan Kirsch; Miodrag Guzvic; Jens Warfsmann; Kamran Honarnejad; Zbigniew Czyz; Isabell Blochberger; Sandra Grunewald; Elisabeth Schneider; Gundula Haunschild; Nina Patwary;

    Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profiled rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identified IL6/PI3K-signaling

    更新日期:2020-05-30
  • Integrative Molecular Characterization of Sarcomatoid and Rhabdoid Renal Cell Carcinoma Reveals Determinants of Poor Prognosis and Response to Immune Checkpoint Inhibitors
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Ziad Bakouny; David A. Braun; Sachet A. Shukla; Wenting Pan; Xin Gao; Yue Hou; Abdallah Flaifel; Stephen Tang; Alice Bosma-Moody; Meng Xiao He; Natalie Vokes; Jackson Nyman; Wanling Xie; Amin H. Nassar; Sarah Abou Alaiwi; Ronan Flippot; Gabrielle Bouchard; John A. Steinharter; Pier Vitale Nuzzo; Miriam Ficial; Miriam Sant'Angelo; Juliet Forman; Jacob E. Berchuck; Shaan Dudani; Kevin Bi; Jihye Park;

    Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors1−3, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize

    更新日期:2020-05-30
  • The MNK1/2-eIF4E axis contributes to phenotype switching, melanoma progression, and resistance to immunotherapy.
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Fan Huang; Christophe Goncalves; Margarita Bartish; Joelle Remy-Sarrazin; Qianyu Guo; Audrey Emond; William Yang; Dany Plourde; Jie Su; Marina Godoy Gimeno; Yao Zhan; Mikhael Attias; Alba Galan; Tomasz rzymski; Milena Mazan; Magdalena Masiejczyk; Jacek Faber; Eli Khoury; Alexandre Benoit; Natascha Gagnon; David Dankort; Ciro A Piccirillo; Fabrice Journe; Ghanem Ghanem; Horacio Uri Saragovi; Nahum Sonenberg;

    Melanomas commonly undergo a phenotype switch, from a proliferative to an invasive state. Melanoma plasticity exhibited as phenotype switching contributes to immunotherapy resistance, however the mechanisms are not completely understood and thus therapeutically unexploited. Here, using a transgenic melanoma mouse model, we demonstrated a critical role of the MNK1/2-eIF4E axis in melanoma plasticity

    更新日期:2020-05-30
  • Tumor-Immune Partitioning and Clustering (TIPC) algorithm reveals distinct signatures of tumor-immune cell interactions within the tumor microenvironment
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Mai Chan Lau; Jennifer Borowsky; Juha P Vayrynen; Koichiro Haruki; Melissa Zhao; Andressa Dias Costa; Simeng Gu; Annacarolina da Silva; Kota Arima; Joe Yeong; Kristen D Felt; Tsuyoshi Hamada; Reiko Nishihara; Jochen K Lennerz; Charles S Fuchs; Catherine J Wu; Shuji Ogino; Jonathan A Nowak

    Growing evidence supports the importance of understanding tumor-immune spatial relationship in the tumor microenvironment in order to achieve precision cancer therapy. However, existing methods, based on oversimplistic cell-to-cell proximity, are largely confounded by immune cell density and are ineffective in capturing tumor-immune spatial patterns. Here we developed a novel computational algorithm

    更新日期:2020-05-30
  • Inhibition of tryptophan-2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Megan R Reed; Leena Maddukuri; Amit Ketkar; Stephanie D. Byrum; Maroof K. Zafar; April C.L. Bostian; Alan J. Tackett; Robert L. Eoff

    Aberrant expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy and immune response in gliomas in part through kynurenine (KYN)-mediated activation of the aryl hydrocarbon receptor (AhR). In the current study, we investigated the hypothesis that TDO activation in gliomas has a broad impact upon genome maintenance - promoting tolerance of replication stress (RS) and repair of

    更新日期:2020-05-30
  • Non-canonical glutamate-cysteine ligase activity protects against ferroptosis
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Yun Pyo Kang; Andrea Mockabee-Macias; Chang Jiang; Isaac S Harris; Gina M DeNicola

    Cysteine is required for maintaining cellular redox homeostasis in both normal and transformed cells. Deprivation of cysteine induces the iron-dependent form of cell death known as ferroptosis; however, the metabolic consequences of cysteine starvation beyond impairment of glutathione synthesis are uncharacterized. Here, we find that cystine starvation promotes ferroptosis not only through the inhibition

    更新日期:2020-05-30
  • ATM Inhibition Synergizes with Fenofibrate in High Grade Serous Ovarian Cancer Cells
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Chi-Wei Chen; Raquel Buj; Erika S Dahl; Kelly E Leon; Katherine M Aird

    Background: Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy in the United States with high grade serous ovarian cancer (HGSOC) as the most commonly diagnosed subtype. While therapies targeting deficiencies in the homologous recombination (HR) pathway are emerging as the standard treatment for HGSOC patients, this strategy is limited to the 50% of patients with a deficiency

    更新日期:2020-05-30
  • Pharmacologically modified pluripotent stem cell-based cancer vaccines with anti-metastatic potential
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Masae Heront-Kishi; Afag Asgorava; Christophe Desterke; Diana Chaker; Marie Ghislaine de Goer; Ali TURHAN; Annelise Bennaceur; Frank Griscelli

    Cancer is maintained by the activity of a rare population of self-renewing cancer stem cells (CSCs), which are resistant to conventional therapies. CSCs share several antigenic determinants with pluripotent stem cells (PSCs). We show here that PSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a model of highly aggressive breast cancer. This

    更新日期:2020-05-30
  • Effects of germline and somatic events in candidate BRCAness genes on breast-tumor signatures
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Weston R Bodily; Brian H Shirts; Tom Walsh; Suleyman Gulsuner; Mary-Claire King; Alyssa Parker; Moom Roosan; Stephen R Piccolo

    Background: Mutations in BRCA1 and BRCA2 cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR

    更新日期:2020-05-30
  • Netrin G1 promotes pancreatic tumorigenesis through cancer associated fibroblast driven nutritional support and immunosuppression
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Ralph Francescone; Débora Barbosa Vendramini-Costa; Janusz Franco-Barraza; Jessica Wagner; Alexander Muir; Allison N Lau; Linara Gabitova; Tatiana Pazina; Sapna Gupta; Tiffany Luong; Neelima Shah; Dustin Rollins; Ruchi Malik; Roshan Thapa; Diana Restifo; Yan Zhou; Kathy Q Cai; Harvey H Hensley; Yinfei Tan; Warren D Kruger; Karthik Devarajan; Siddharth Balachandran; Andres J Klein-Szanto; Huamin Wang;

    Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate and lacks effective therapeutics. Therefore, it is of paramount importance to identify new targets. Using multi-plex data from patient tissue, three-dimensional co-culturing in vitro assays, and orthotopic murine models, we identified Netrin G1 (NetG1) as a promoter of PDAC tumorigenesis. NetG1+ cancer-associated fibroblasts (CAFs)

    更新日期:2020-05-30
  • N-acetylaspartate improves cell survival when glucose is limiting
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    H. Furkan Alkan; Katharina Eva Walter; Hubert Hackl; Matthew Vander Heiden; Tobias Madl; Juliane Bogner-Strauss

    N-acetylasparate (NAA), previously considered a brain-specific metabolite, is found in several cancers. However, whether it plays a role in tumor growth or survival is not fully understood. We provide evidence that NAA prevents cell death in low-glucose conditions via sustaining intracellular UDP-N-acetylglucosamine (UDP-GlcNac) levels, suppressing endoplasmic reticulum (ER) stress, and enabling continued

    更新日期:2020-05-30
  • Ablation of MYB-dependent leukaemia phenotype in MLL-driven AML correlates with increased expression of MAFB.
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Carl Ward; Pierre Cauchy; David S Walton; Mary L Clarke; Daniel Blakemore; Florian Grebien; Paloma Garcia; Jon Frampton; Giacomo Volpe

    The transcription factor MYB plays a pivotal role in haematopoietic homeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). Our previous work has demonstrated that not all AML types display the same dependency on MYB expression and that MYB dependence is dictated by the nature of the driver mutation. However, whether this difference in MYB

    更新日期:2020-05-30
  • Hypoxia driven oncometabolite L-2HG maintains "stemness"-differentiation balance and facilitates immune suppression in pancreatic cancer
    bioRxiv. Cancer Biol. Pub Date : 2020-05-30
    Vineet K Gupta; Nikita S Sharma; Brittany Durden; Vanessa T Garrido; Kousik Kesh; Dujon Edwards; Dezhen Wang; Ciara Myers; Sanjoy K Bhattacharya; Ashok Saluja; Pankaj K Singh; Sulagna Banerjee

    2-hydroxyglutarate (2-HG) has gained considerable importance in glioma and blood cancers that have mutations in the IDH1/2 gene. In the current study we show for the first time that pancreatic tumors produce 2HG in the absence of IDH1/2 mutation. Our study shows that hypoxic pancreatic tumors that have activated lactate dehydrogenase (LDH) activity, produce the L-isoform of 2HG. Metabolic mass spectrometric

    更新日期:2020-05-30
  • Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
    bioRxiv. Cancer Biol. Pub Date : 2020-05-29
    Corrine Nief; Robert Morhard; Erika Chelales; Daniel Adrianzen Alvarez; Ioanna Bourla; Christopher T Lam; Brian Crouch; Alan A Sag; Jenna L Mueller; David Katz; Mark W Dewhirst; Jeffrey I Everitt; Nirmala Ramanujam

    Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of

    更新日期:2020-05-29
  • Identification of oncolytic vaccinia restriction factors in canine high-grade mammary tumor cells using single-cell transcriptomics
    bioRxiv. Cancer Biol. Pub Date : 2020-05-29
    Beatrice Cambien; Kevin Lebrigand; Alberto Baeri; Nicolas Nottet; Catherine Compin; Audrey Lamit; Olivier Ferraris; Christophe Peyrefitte; Virginie Magnone; Jerome Henriques; Laure-Emmanuelle Zaragosi; Sophie Giorgetti-Peraldi; Frederic Bost; Marine Gautier-Isola; Roger Rezzonico; Pascal Barbry; Robert Barthel; Bernard Mari; Georges Vassaux

    Mammary carcinoma, including triple-negative breast carcinomas (TNBC) are tumor-types for which human and canine pathologies are closely related at the molecular level. Low-passage, primary carcinoma cells from TNBC versus non-TNBC were used to compare the efficacy of an oncolytic vaccinia virus (VV). We show that non-TNBC cells are 28 times more sensitive to VV than TNBC cells in which VV replication

    更新日期:2020-05-29
  • Oncogenic mutation or overexpression of oncogenic KRAS or BRAF is not sufficient to confer oncogene addiction.
    bioRxiv. Cancer Biol. Pub Date : 2020-05-29
    Reina E Ito; Chitose Oneyama; Kazuhiro Aoki

    Oncogene addiction is a cellular property by which cancer cells become highly dependent on the expression of oncogenes for their survival. Oncogene addiction can be exploited to design molecularly targeted drugs that kill only cancer cells by inhibiting the specific oncogenes. Genes and cell lines exhibiting oncogene addiction, as well as the mechanisms by which cell death is induced when addicted

    更新日期:2020-05-29
  • SARS-CoV-2 infection induces EMT-like molecular changes, including ZEB1-mediated repression of the viral receptor ACE2, in lung cancer models
    bioRxiv. Cancer Biol. Pub Date : 2020-05-29
    C. Allison Stewart; Carl M. Gay; Kavya Ramkumar; Kasey R. Cargill; Robert J. Cardnell; Monique B. Nilsson; Simon Heeke; Elizabeth M. Park; Samrat T. Kundu; Lixia Diao; Qi Wang; Li Shen; Yuanxin Xi; Carminia Maria Della Corte; Youhong Fan; Kiran Kundu; Curtis R Pickering; Faye M Johnson; Jianjun Zhang; Humam Kadara; John D. Minna; Don L. Gibbons; Jing Wang; John V. Heymach; Lauren Averett Byers

    COVID-19 is an infectious disease caused by SARS-CoV-2, which enters host cells via the cell surface proteins ACE2 and TMPRSS2. Using normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation of ACE2 and TMPRSS2. We find that ACE2 expression is restricted to a select population of highly epithelial cells and is repressed by

    更新日期:2020-05-29
  • In silico analysis of SNPs in human phosphofructokinase, Muscle (PFKM) gene: An apparent therapeutic target of aerobic glycolysis and cancer
    bioRxiv. Cancer Biol. Pub Date : 2020-05-29
    Yogita Rani; Kamaljit Kaur; Madhvi Sharma; Namarta Kalia

    Phosphofructokinase, muscle (PFKM), a key glycolytic regulatory enzyme is a potential target for cancer therapeutic studies accredited to the employed inefficient phenomenon known as Warburg effect. PFKM is encoded by PFKM gene located at chromosome 12q13.11. Single nucleotide polymorphisms (SNPs) are known to profoundly affect gene expression and protein function. Therefore, the first attempt was

    更新日期:2020-05-29
  • Sustained Androgen Receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis
    bioRxiv. Cancer Biol. Pub Date : 2020-05-29
    Min Ma; Soumitra Ghosh; Daniele Tavernari; Atul Katarkar; Andrea Clocchiatti; Luigi Mazzeo; Anastasia Samarkina; Justine Epiney; Yi-Ru Yu; Ping-Chih Ho; Mitchell P Levesque; Berna Özdemir; Giovanni Ciriello; Reinhard Dumme; Gian-Paolo Dotto

    Melanoma is a benchmark of major clinical significance for cancer development with greater aggressiveness in the male than the female population. Surprisingly little is known on the role of androgen receptor (AR) signaling in the disease. Irrespectively of expression levels, genetic and pharmacological suppression of AR activity in a large panel of melanoma cells, derived from both male and female

    更新日期:2020-05-29
  • Novel mechanistic targets of Forkhead box Q1 transcription factor in human breast cancer cells
    bioRxiv. Cancer Biol. Pub Date : 2020-05-29
    Su-Hyeong Kim; Eun-Ryeong Hahm; Krishna B Singh; Shivendra V. Singh

    The transcription factor forkhead box Q1 (FoxQ1), which is overexpressed in different solid tumors, has emerged as a key player in the pathogenesis of breast cancer by regulating epithelial-mesenchymal transition, maintenance of cancer-stem like cells, and metastasis. However, the mechanism underlying oncogenic function of FoxQ1 is still not fully understood. In this study, we compared the RNA-seq

    更新日期:2020-05-29
  • Laminin N-terminus α31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion.
    bioRxiv. Cancer Biol. Pub Date : 2020-05-28
    Lee D Troughton; Tobias Zech; Kevin J Hamill

    Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive

    更新日期:2020-05-28
  • In vivo deuterated water labeling allows tumor visualization via deuterium magnetic resonance spectroscopic imaging of cholesterol
    bioRxiv. Cancer Biol. Pub Date : 2020-05-28
    Julian C. Assmann; Jeffrey R. Brender; Don E. Farthing; Keita Saito; Kathrynne A. Warrick; Natella Maglakelidze; Daniel R. Crooks; Hellmut Merkle; Murali C. Krishna; Ronald E. Gress; Nataliya P. Buxbaum

    Water is an essential component of many biochemical reactions. Deuterated water (D2O) has been used to study cell kinetics, protein synthesis, and metabolism. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with deuterium due to high metabolic activity, thus allowing imaging of biosynthetically labeled metabolites within tumors in vivo. We initiated systemic

    更新日期:2020-05-28
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