300,194 results match your criteria Cancer Biology & Therapy [Journal]


EpigenCentral: Portal for DNA methylation data analysis and classification in rare diseases.

Hum Mutat 2020 Jul 5. Epub 2020 Jul 5.

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.

Epigenetic processes play a key role in regulating gene expression. Genetic variants that disrupt chromatin-modifying proteins are associated with a broad range of diseases, some of which have specific epigenetic patterns, such as aberrant DNA methylation, that may be used as disease biomarkers. While much of the epigenetic research has focused on cancer, there is a paucity of resources devoted to neurodevelopmental disorders, which include autism spectrum disorder and many rare, clinically overlapping syndromes. Read More

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http://dx.doi.org/10.1002/humu.24076DOI Listing

Variant effect on splicing regulatory elements, branchpoint usage, and pseudoexonization: strategies to enhance bioinformatic prediction using hereditary cancer genes as exemplars.

Hum Mutat 2020 Jul 5. Epub 2020 Jul 5.

Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.

It is possible to estimate the prior probability of pathogenicity for germline disease gene variants based on bioinformatic prediction of variant effect/s. However, routinely used approaches have likely led to the underestimation and underreporting of variants located outside donor and acceptor splice site motifs that affect mRNA processing. This review presents information about hereditary cancer gene germline variants, outside native splice sites, with experimentally validated splicing effects. Read More

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http://dx.doi.org/10.1002/humu.24074DOI Listing

Secondary metabolites from acridocarpus orientalis inhibits 4T1 cells and promotes mesenchymal stem cells (MSCs) proliferation.

Mol Biol Rep 2020 Jul 4. Epub 2020 Jul 4.

Laboratory for Stem Cell & Regenerative Medicine, Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box: 33, Nizwa, PC, 616, Oman.

Among medicinal plants, Acridocarpus orientalis (AO) possesses a remarkable anti-cancer potential, possibly because of its anti-oxidant property. In this study, the leaf and stem extracts from AO were assessed to find the bioactive compound with selective anti-cancer properties. The MTT viability and live and dead assays revealed that around 80% and 98% of 4T1 cells survival were declined after 48 h incubation with leaf and stem extracts, respectively. Read More

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http://dx.doi.org/10.1007/s11033-020-05632-yDOI Listing

Extrahepatic metabolism of ibrutinib.

Invest New Drugs 2020 Jul 4. Epub 2020 Jul 4.

Division of Pharmacoepidemiology & Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.

Ibrutinib is a first-in-class Bruton's kinase inhibitor used in the treatment of multiple lymphomas. In addition to CYP3A4-mediated metabolism, glutathione conjugation can be observed. Subsequently, metabolism of the conjugates and finally their excretion in feces and urine occurs. Read More

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http://dx.doi.org/10.1007/s10637-020-00970-xDOI Listing

Synaptic Input to Brain Tumors: Clinical Implications.

Neuro Oncol 2020 Jul 5. Epub 2020 Jul 5.

Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, INF, Heidelberg.

The recent discovery of synaptic connections between neurons and brain tumor cells fundamentally challenges our understanding of gliomas and brain metastases, and shows how these tumors can integrate into complex neuronal circuits. Here, we provide an overview on glutamatergic neuron-to-brain tumor synaptic communication (NBTSC) and explore novel therapeutic avenues. First, we summarize current concepts of direct synaptic interactions between presynaptic neurons and postsynaptic glioma cells, and indirect perisynaptic input to metastatic breast cancer cells. Read More

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http://dx.doi.org/10.1093/neuonc/noaa158DOI Listing

Patients with Head-and-Neck Cancer: Dysphagia and Affective Symptoms.

Folia Phoniatr Logop 2020 Jul 3:1-8. Epub 2020 Jul 3.

Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.

Objective: Affective symptoms are common in patients with head-and-neck cancer. This study determined the association between the presence of aspiration and symptoms of anxiety and depression, as well as patient characteristics in patients with head-and-neck cancer and dysphagia.

Methods: Eighty-four patients with head-and-neck cancer and dysphagia completed the Hospital Anxiety and Depression Scale and underwent a standardized fiberoptic endoscopic evaluation of swallowing. Read More

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http://dx.doi.org/10.1159/000508367DOI Listing

The roles of miRNAs' clinical efficiencies in the colorectal cancer pathobiology: A review article.

Hum Antibodies 2020 Jun 22. Epub 2020 Jun 22.

Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

MiRNAs (microRNAs) are defined as micro directors and regulators of gene expression. Since altered miRNA expression is signified in the pathobiology of diverse cancers such as colorectal cancers (CRCs), these molecules are described as therapeutic targets, either. Manipulation of miRNAs could lead to further therapy for chemo and radio-resistant CRCs. Read More

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http://dx.doi.org/10.3233/HAB-200417DOI Listing

Identification of let-7f-5p as a novel biomarker of recurrence in non-muscle invasive bladder cancer.

Cancer Biomark 2020 Jun 28. Epub 2020 Jun 28.

Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.

Background: Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), 30% to 70% experience recurrences within 6 to 12 years of diagnosis. The need to screen for these events every 3 to 6 months and ultimately annually by cystoscopy makes bladder cancer one of the most expensive malignancies to manage.

Objective: The of this study was to identify reproducible prognostic microRNAs in resected non-muscle invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype as potential biomarkers and molecular therapeutic targets. Read More

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http://dx.doi.org/10.3233/CBM-191322DOI Listing

Generation of human induced pluripotent stem cell line from Alzheimer's disease patient with PSEN2 N141I mutation using integration-free non-viral method.

Stem Cell Res 2020 Jun 29;47:101892. Epub 2020 Jun 29.

Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea; Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.

Induced pluripotent stem cell (iPSC) line HUi001-A was reprogrammed from skin fibroblasts via non-integrating, virus free self-replicating RNA. Skin fibroblasts from an 81-year-old female Caucasian familial Alzheimer's disease patient of Volga German family carrying N141I mutation in the PSEN2 gene (familial AD4, clinical summary confirmed Alzheimer's disease) was obtained from the Coriell Institute (AG09908). Generated iPSCs were characterized and pluripotency was confirmed. Read More

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http://dx.doi.org/10.1016/j.scr.2020.101892DOI Listing

Electron Transport Chain Complex II Regulates Steroid Metabolism.

iScience 2020 Jun 20;23(7):101295. Epub 2020 Jun 20.

Department of Chemistry, University of Alberta, Edmonton, Canada.

The first steroidogenic enzyme, cytochrome P450-side-chain-cleavage (SCC), requires electron transport chain (ETC) complexes III and IV to initiate steroid metabolic processes for mammalian survival. ETC complex II, containing succinate dehydrogenase (quinone), acts with the TCA cycle and has no proton pumping capacity. We show that complex II is required for SCC activation through the proton pump, generating an intermediate state for addition of phosphate by succinate. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101295DOI Listing

Identifying States of Collateral Sensitivity during the Evolution of Therapeutic Resistance in Ewing's Sarcoma.

iScience 2020 Jun 20;23(7):101293. Epub 2020 Jun 20.

Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Systems Biology and Bioinformatics Department, School of Medicine, Case Western Reserve University, Cleveland OH 44106, USA; Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH 44106, USA. Electronic address:

Advances in the treatment of Ewing's sarcoma (EWS) are desperately needed, particularly in the case of metastatic disease. A deeper understanding of collateral sensitivity, where the evolution of therapeutic resistance to one drug aligns with sensitivity to another drug, may improve our ability to effectively target this disease. For the first time in a solid tumor, we produced a temporal collateral sensitivity map that demonstrates the evolution of collateral sensitivity and resistance in EWS. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101293DOI Listing

Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells.

iScience 2020 Jun 20;23(7):101289. Epub 2020 Jun 20.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Chronic stress-related hormones modulate tumor pathogenesis at multiple levels; however, the molecular pathways involved in stress and cervical cancer progression are not well understood. We established a preclinical orthotopic mouse model of cervical cancer and used the model to show that daily restraint stress increased tumor growth and metastatic tumor burden. Exposure to norepinephrine significantly protected cervical cancer cells from anoikis. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101289DOI Listing

Skp2 Depletion Reduces Tumor-Initiating Properties and Promotes Apoptosis in Synovial Sarcoma.

Transl Oncol 2020 Jul 2;13(10):100809. Epub 2020 Jul 2.

Department of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. Electronic address:

Synovial sarcoma (SS) is an aggressive soft-tissue cancer with a poor prognosis and a propensity for local recurrence and distant metastasis. In this study, we investigated whether S phase kinase-associated protein (Skp2) plays an oncogenic role in tumor initiation, progression, and metastasis of SS. Our study revealed that Skp2 is frequently overexpressed in SS specimens and SS18-SSX transgenic mouse tumors, as well as correlated with clinical stages. Read More

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http://dx.doi.org/10.1016/j.tranon.2020.100809DOI Listing

The recent advances in non-homologous end-joining through the lens of lymphocyte development.

DNA Repair (Amst) 2020 Jun 25;94:102874. Epub 2020 Jun 25.

Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY 10032, United States; Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY 10032, United States; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY 10032, United States; Department of Immunology and Microbiology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY 10032, United States. Electronic address:

Lymphocyte development requires ordered assembly and subsequent modifications of the antigen receptor genes through V(D)J recombination and Immunoglobulin class switch recombination (CSR), respectively. While the programmed DNA cleavage events are initiated by lymphocyte-specific factors, the resulting DNA double-strand break (DSB) intermediates activate the ATM kinase-mediated DNA damage response (DDR) and rely on the ubiquitously expressed classical non-homologous end-joining (cNHEJ) pathway including the DNA-dependent protein kinase (DNA-PK), and, in the case of CSR, also the alternative end-joining (Alt-EJ) pathway, for repair. Correspondingly, patients and animal models with cNHEJ or DDR defects develop distinct types of immunodeficiency reflecting their specific DNA repair deficiency. Read More

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http://dx.doi.org/10.1016/j.dnarep.2020.102874DOI Listing

Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery.

Nanomedicine 2020 Jul 2:102262. Epub 2020 Jul 2.

Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.; Department of Ophthalmology, Massey Cancer Center, Center for Pharmaceutical Engineering, and Institute for Structural Biology, Drug Discovery & Development (ISB3D), Virginia Commonwealth University, Richmond, VA 23298, USA.. Electronic address:

Tenacious sputum poses a critical diffusion barrier for aerosol antibiotics used to treat cystic fibrosis (CF) lung infection. We conducted a proof-of-concept study using dense poly(ethylene glycol) coated polystyrene nanoparticles (PS-PEG NPs) as model muco-inert particles (MIP) formulated as a powder using an excipient enhanced growth (EEG) strategy, aiming to minimize extrathoracic airway loss, maximize deposition in the airway and further overcome the sputum barrier in the CF lungs. The EEG aerosol formulation containing PS-PEG MIP was prepared by spray drying and produced discrete spherical particles with geometric diameter of approximately 2μm; and>80% of the powder dose was delivered from a new small-animal dry powder inhaler (DPI). Read More

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http://dx.doi.org/10.1016/j.nano.2020.102262DOI Listing

Liquid biopsy in ovarian cancer.

Clin Chim Acta 2020 Jul 2. Epub 2020 Jul 2.

School of Biotechnology, National Institute of Technology, Calicut-673601, Kerala, India. Electronic address:

Ovarian cancer is typically diagnosed at an advanced stage and poses a significant challenge to treatment and recovery. Relapsed ovarian cancer and chemoresistance of ovarian tumor cells are other clinical challenges. Liquid biopsy is an essential non-invasive diagnostic test that evaluates circulating tumor cells and tumor DNA, as well as other blood markers that may be useful in guiding precision medicine. Read More

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http://dx.doi.org/10.1016/j.cca.2020.06.047DOI Listing

E3 ligase SCF ubiquitinates and degrades tumor suppressor C/EBPα in acute myeloid leukemia.

Life Sci 2020 Jul 2:118041. Epub 2020 Jul 2.

Room No. LSS008, Division of Cancer Biology, CSIR-Central Drug Research Institute, CDRI Sector-10, Jankipuram Extension, Lucknow, 226031, UP, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India. Electronic address:

Aim: Transcription factor CCAAT/Enhancer binding protein alpha (C/EBPα) is a key regulator of myeloid differentiation, granulopoiesis in particular. Although CEBPA mutations are found in more than 10% in AML, functional inhibition of C/EBPα protein is also widely observed in AML. Here, we sought to examine if SKP2, an aberrantly enhanced E3 ubiquitin ligase in primary AMLs inhibits C/EBPα stability to induce differentiation block. Read More

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http://dx.doi.org/10.1016/j.lfs.2020.118041DOI Listing
July 2020
2.702 Impact Factor

FK506 binding proteins and inflammation related signalling pathways; basic biology, current status and future prospects for pharmacological intervention.

Pharmacol Ther 2020 Jul 2:107623. Epub 2020 Jul 2.

School of Pharmacy and Biomolecular Sciences, Irish Centre for Vascular Biology, RCSI University of Medicine and Health Sciences, Dublin, Ireland. Electronic address:

FK506 binding (FKBP) proteins are part of the highly conserved immunophilin family and its members have fundamental roles in the regulation of signalling pathways involved in inflammation, adaptive immune responses, cancer and developmental biology. The original member of this family, FKBP12, is a well-known binding partner for the immunosuppressive drugs tacrolimus (FK506) and sirolimus (rapamycin). FKBP12 and its analog, FKBP12. Read More

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http://dx.doi.org/10.1016/j.pharmthera.2020.107623DOI Listing

Implications for glycosylated compounds and their anti-cancer effects.

Int J Biol Macromol 2020 Jul 2. Epub 2020 Jul 2.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Glycosylated compounds are major secondary metabolites of plants, which have various therapeutic effects on human diseases, by acting as anti-cancer, antioxidant, and anti-inflammatory agents. Glycosylation increases stability, bioactivity, and solubility of compounds and improves their pharmacological properties. Two well-known examples of glycosylated compounds include cardiac and flavonoid, the anti-tumor activities of which have been emphasized by several studies. Read More

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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.281DOI Listing

Programmed Cell Death-Ligand 2: A Neglected But Important Target in the Immune Response to Cancer?

Transl Oncol 2020 Jul 1;13(10):100811. Epub 2020 Jul 1.

Columbia University Medical Center, Columbia Center for Translational Immunology, New York, NY, USA. Electronic address:

Programmed cell death-ligand 2 (PD-L2) is one of the two ligands of the programmed cell death-1 (PD-1) receptor, an inhibitory protein mainly expressed on activated immune cells that is targeted in the clinic, with successful and remarkable results. The PD-1/PD-Ls axis was shown to be one of the most relevant immunosuppressive pathways in the immune microenvironment, and blocking this interaction gave rise to an impressive clinical benefit in a broad variety of solid and hematological malignancies. Although PD-L2 has been historically considered a minor ligand, it binds to PD-1 with a two- to six-fold higher affinity as compared to PD-L1. Read More

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http://dx.doi.org/10.1016/j.tranon.2020.100811DOI Listing

Immune Cell Associations with Cancer Risk.

iScience 2020 Jun 20;23(7):101296. Epub 2020 Jun 20.

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain. Electronic address:

Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101296DOI Listing

Prognostic prediction of carcinoma by a differential-regulatory-network-embedded deep neural network.

Comput Biol Chem 2020 Jun 24;88:107317. Epub 2020 Jun 24.

School of Computer Science and Technology, Harbin Institute of Technology (Shenzhen), Shenzhen, Guangdong 518055, China; School of Computer Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China. Electronic address:

The accurate prognostic prediction is essential for precise diagnosis and treatment of carcinoma. In addition to clinical survival prediction method, many computational methods based on transcriptomic data have been proposed to build the prediction models and study the prognosis of cancer patients. We propose a differential-regulatory-network-embedded deep neural network (DRE-DNN) method by integrating differential regulatory analysis based on gene co-expression network and deep neural network (DNN) method. Read More

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http://dx.doi.org/10.1016/j.compbiolchem.2020.107317DOI Listing

Lipid nanoparticle technology for therapeutic gene regulation in the liver.

Adv Drug Deliv Rev 2020 Jul 1. Epub 2020 Jul 1.

Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.

Hereditary genetic disorders, cancer, and infectious diseases of the liver affect millions of people around the globe and are a major public health burden. Most contemporary treatments offer limited relief as they generally aim to alleviate disease symptoms. Targeting the root cause of diseases originating in the liver by regulating malfunctioning genes with nucleic acid-based drugs s holds great promise as a therapeutic approach. Read More

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http://dx.doi.org/10.1016/j.addr.2020.06.026DOI Listing

Engineering functional microvessels in synthetic polyurethane random-pore scaffolds by harnessing perfusion flow.

Biomaterials 2020 Jun 23;256:120183. Epub 2020 Jun 23.

Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada; Faculty of Dentistry, University of Toronto, Toronto, Canada. Electronic address:

Recently reported biomaterial-based approaches toward prevascularizing tissue constructs rely on biologically or structurally complex scaffolds that are complicated to manufacture and sterilize, and challenging to customize for clinical applications. In the current work, a prevascularization method for soft tissue engineering that uses a non-patterned and non-biological scaffold is proposed. Human fibroblasts and HUVECs were seeded on an ionomeric polyurethane-based hydrogel and cultured for 14 days under medium perfusion. Read More

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http://dx.doi.org/10.1016/j.biomaterials.2020.120183DOI Listing

Hydroxychloroquine-Loaded Hollow Mesoporous Silica Nanoparticles for Enhanced Autophagy Inhibition and Radiation Therapy.

J Control Release 2020 Jul 1. Epub 2020 Jul 1.

Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea. Electronic address:

Radiotherapy (RT) is a major modality for cancer treatment, along with surgery and chemotherapy. Despite its therapeutic effect, the recurrence and metastasis of tumors due to the acquired resistance of cancer cells to RT remain significant clinical problems. Therefore, it is imperative to overcome radioresistance and improve radiosensitivity in cancer patients. Read More

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http://dx.doi.org/10.1016/j.jconrel.2020.06.025DOI Listing

Epithelial cadherin regulates transition between the naïve and primed pluripotent states in mouse embryonic stem cells.

Stem Cells 2020 Jul 4. Epub 2020 Jul 4.

Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.

Inhibition of E-cad in mouse embryonic stem cells (mESCs) leads to a switch from LIF-BMP to Activin/Nodal-dependent pluripotency, consistent with transition from a naïve to primed pluripotent phenotype. We have used both genetic ablation and steric inhibition of E-cad function in mESCs to assess alterations to phenotype using quantitative mass spectrometry analysis, network models, and functional assays. Proteomic analyses revealed that one third of detected proteins were altered in E-cad null mESCs (Ecad mESCs) compared to wild type (624 proteins were downregulated and 705 were proteins upregulated). Read More

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http://dx.doi.org/10.1002/stem.3249DOI Listing

miR-181a overexpression predicts the poor treatment response and early-progression of serous ovarian cancer patients.

Int J Cancer 2020 Jul 4. Epub 2020 Jul 4.

Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.

Ovarian cancer (OC) remains a leading cause of gynecological cancer-related death worldwide, characterized by poor 5-year survival. Molecular markers could serve as crucial tools of personalized prognosis and therapy. Herein, we present miR-181a as novel predictor of OC prognosis, using five independent OC cohorts. Read More

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http://dx.doi.org/10.1002/ijc.33182DOI Listing

Oral microbial dysbiosis and its performance in predicting oral cancer.

Carcinogenesis 2020 Jul 4. Epub 2020 Jul 4.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Dysbiosis of oral microbiome may dictate the progression of oral squamous cell carcinoma (OSCC). Yet, the composition of oral microbiome fluctuates by saliva and distinct sites of oral cavity and is affected by risky behaviors (smoking, drinking, and betel quid chewing) and individuals' oral health condition. To characterize the disturbances in the oral microbial population mainly due to oral tumorigenicity, we profiled the bacteria within the surface of OSCC lesion and its contralateral normal tissue from discovery (n=74) and validation (n=42) cohorts of male patients with cancers of the buccal mucosa. Read More

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http://dx.doi.org/10.1093/carcin/bgaa062DOI Listing

Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma.

Glia 2020 Jul 4. Epub 2020 Jul 4.

Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. Read More

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http://dx.doi.org/10.1002/glia.23866DOI Listing

The role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a Position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).

Eur J Heart Fail 2020 Jul 4. Epub 2020 Jul 4.

National Heart and Lung Institute, Imperial College, London, United Kingdom.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. Read More

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http://dx.doi.org/10.1002/ejhf.1957DOI Listing

On precision dosing of oral small molecule drugs in oncology.

Br J Clin Pharmacol 2020 Jul 4. Epub 2020 Jul 4.

Departments of Pathology & Cell Biology and Medicine, Columbia University Irving Medical Center, New York, NY, 10032, United States of America.

Personalization of oral small molecule anticancer drug doses based on individual patient blood drug levels, also known as therapeutic drug monitoring or TDM, has the potential to significantly improve the effectiveness of treatment by maximizing drug efficacy and minimize toxicity. However, this option has not yet been widely embraced by the oncology community. Some reasons for this include increased logistical complexity of dose individualization, the lack of clinical laboratories that measure small molecule drug concentrations in support of patient care, and the lack of reimbursement of costs. Read More

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http://dx.doi.org/10.1111/bcp.14454DOI Listing

[Emerging roles of Hippo signaling pathway in gastrointestinal cancers and its molecular mechanisms].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 May;49(1):35-43

Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.

Hippo signaling pathway is highly conservative in evolution. MST1/2, LATS1/2, and the effector protein YAP/TAZ are the core members of this signaling pathway in mammalian cells. There have been many studies on YAP/TAZ and its downstream, however, the upstream regulatory factors of the Hippo signaling pathway remain unclear, and become one of the hot research directions of this pathway at present. Read More

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Challenges of Engineering Biomimetic Dental and Paradental Tissues.

Tissue Eng Regen Med 2020 Jul 3. Epub 2020 Jul 3.

Department of Dental Biomaterials, Faculty of Dentistry, Mansoura University, Elgomhouria St., Mansoura, 35516, Egypt.

Background: Loss of the dental and paradental tissues resulting from trauma, caries or from systemic diseases considered as one of the most significant and frequent clinical problem to the healthcare professionals. Great attempts have been implemented to recreate functionally, healthy dental and paradental tissues in order to substitute dead and diseased tissues resulting from secondary trauma of car accidents, congenital malformations of cleft lip and palate or due to acquired diseases such as cancer and periodontal involvements.

Method: An extensive literature search has been done on PubMed database from 2010 to 2019 about the challenges of engineering a biomimetic tooth (BioTooth) regarding basic biology of the tooth and its supporting structures, strategies, and different techniques of obtaining biological substitutes for dental tissue engineering. Read More

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http://dx.doi.org/10.1007/s13770-020-00269-1DOI Listing

Autophagy inhibition impairs the invasion potential of medulloblastoma cells.

Mol Biol Rep 2020 Jul 3. Epub 2020 Jul 3.

Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.

Medulloblastoma, a highly malignant pediatric brain tumor, consists of four distinct molecular subgroups called WNT, SHH, Group 3, and Group 4 that differ in their clinical characteristics with the WNT subgroup having excellent survival rate. About 1/3rd medulloblastomas have metastasis at the time of diagnosis suggesting, high invasion potential of these tumors. We have earlier reported that the tumor-suppressive role of miR-204 and miR-30a is accompanied by inhibition of autophagy in medulloblastoma cells. Read More

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http://dx.doi.org/10.1007/s11033-020-05603-3DOI Listing

Evaluation of the Effects of Valproic Acid Treatment on Cell Survival and Epithelial-Mesenchymal Transition-Related Features of Human Gastric Cancer Cells.

J Gastrointest Cancer 2020 Jul 3. Epub 2020 Jul 3.

Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran.

Purpose: Metastasis is the most important feature of gastric cancer accounting for more than 90% of tumor-related mortality. As one of the main modulators of epithelial-mesenchymal transition (EMT), histone deacetylase inhibitors (HDACI) are considered rational candidates for cancer therapy. Valproic acid (VPA) is a HDACI with reported controversial effects on the EMT. Read More

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http://dx.doi.org/10.1007/s12029-019-00332-8DOI Listing

Serum levels of the IL-6 family of cytokines predict prognosis in renal cell carcinoma (RCC).

Cancer Immunol Immunother 2020 Jul 3. Epub 2020 Jul 3.

Surgical Clinic, Department of Urology, Haukeland University Hospital, 5021, Bergen, Norway.

Purpose: An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival.

Methods: A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. Read More

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http://dx.doi.org/10.1007/s00262-020-02655-zDOI Listing

Lymphoma Predisposing Gene in an Extended Family: CD70 Signaling Defect.

J Clin Immunol 2020 Jul 3. Epub 2020 Jul 3.

Aziz Sancar Institute of Experimental Medicine, Genetics Department, Istanbul University, Istanbul, Turkey.

Genome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Read More

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http://dx.doi.org/10.1007/s10875-020-00816-4DOI Listing

Receptor conversion in metastatic breast cancer: analysis of 390 cases from a single institution.

Mod Pathol 2020 Jul 3. Epub 2020 Jul 3.

Department of Pathology, The University of Alabama Birmingham, Birmingham, AL, USA.

Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status provide clinical utility in guiding therapeutic decision-making in metastatic breast cancer (BC). Increasing data have shown substantial differences between the receptor profiles of primary BCs and their paired metastases. In this study, we provide a large single center cohort to assess the frequency of receptor conversion in metastatic BC. Read More

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http://dx.doi.org/10.1038/s41379-020-0615-zDOI Listing

Rapid activation of distinct members of multigene families in Plasmodium spp.

Commun Biol 2020 Jul 3;3(1):351. Epub 2020 Jul 3.

School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

The genomes of Plasmodium spp. encode a number of different multigene families that are thought to play a critical role for survival. However, with the exception of the P. Read More

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http://dx.doi.org/10.1038/s42003-020-1081-3DOI Listing

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Nat Commun 2020 Jul 3;11(1):3353. Epub 2020 Jul 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. Read More

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http://dx.doi.org/10.1038/s41467-020-16483-3DOI Listing

Persistent telomere cohesion protects aged cells from premature senescence.

Nat Commun 2020 Jul 3;11(1):3321. Epub 2020 Jul 3.

Kimmel Center for Biology and Medicine at the Skirball Institute, Department of Pathology, New York University School of Medicine, New York, NY, 10016, USA.

Human telomeres are bound by the telomere repeat binding proteins TRF1 and TRF2. Telomere shortening in human cells leads to a DNA damage response that signals replicative senescence. While insufficient loading of TRF2 at shortened telomeres contributes to the DNA damage response in senescence, the contribution of TRF1 to senescence induction has not been determined. Read More

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http://dx.doi.org/10.1038/s41467-020-17133-4DOI Listing

Rare variant of the epigenetic regulator SMCHD1 in a patient with pituitary hormone deficiency.

Sci Rep 2020 Jul 3;10(1):10985. Epub 2020 Jul 3.

Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.

Isolated hypogonadotropic hypogonadism (IHH), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) constitute a disease spectrum whose etiology remains largely unknown. This study aimed to clarify whether mutations in SMCHD1, an epigenetic regulator gene, might underlie this disease spectrum. SMCHD1 is a causative gene for Bosma arhinia microphthalmia syndrome characterized by arhinia, microphthalmia and IHH. Read More

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http://dx.doi.org/10.1038/s41598-020-67715-xDOI Listing

Characterization of an alternative BAK-binding site for BH3 peptides.

Nat Commun 2020 Jul 3;11(1):3301. Epub 2020 Jul 3.

Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.

Many cellular stresses are transduced into apoptotic signals through modification or up-regulation of the BH3-only subfamily of BCL2 proteins. Through direct or indirect mechanisms, these proteins activate BAK and BAX to permeabilize the mitochondrial outer membrane. While the BH3-only proteins BIM, PUMA, and tBID have been confirmed to directly activate BAK through its canonical BH3 binding groove, whether the BH3-only proteins BMF, HRK or BIK can directly activate BAK is less clear. Read More

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http://dx.doi.org/10.1038/s41467-020-17074-yDOI Listing

A sequential methodology for the rapid identification and characterization of breast cancer-associated functional SNPs.

Nat Commun 2020 Jul 3;11(1):3340. Epub 2020 Jul 3.

Aging Institute, University of Pittsburgh, Pittsburgh, PA, 15219, USA.

GWAS cannot identify functional SNPs (fSNP) from disease-associated SNPs in linkage disequilibrium (LD). Here, we report developing three sequential methodologies including Reel-seq (Regulatory element-sequencing) to identify fSNPs in a high-throughput fashion, SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify fSNP-bound proteins and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to detect allele-specific protein:fSNP binding. We first apply Reel-seq to screen a library containing 4316 breast cancer-associated SNPs and identify 521 candidate fSNPs. Read More

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http://dx.doi.org/10.1038/s41467-020-17159-8DOI Listing

An ecological framework to understand the efficacy of fecal microbiota transplantation.

Nat Commun 2020 Jul 3;11(1):3329. Epub 2020 Jul 3.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.

Human gut microbiota plays critical roles in physiology and disease. Our understanding of ecological principles that govern the dynamics and resilience of this highly complex ecosystem remains rudimentary. This knowledge gap becomes more problematic as new approaches to modifying this ecosystem, such as fecal microbiota transplantation (FMT), are being developed as therapeutic interventions. Read More

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http://dx.doi.org/10.1038/s41467-020-17180-xDOI Listing

NRAS mutant E132K identified in young-onset sporadic colorectal cancer and the canonical mutants G12D and Q61K affect distinct oncogenic phenotypes.

Sci Rep 2020 Jul 3;10(1):11028. Epub 2020 Jul 3.

Disease Molecular Biology and Epigenetics Laboratory, National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Ma. Regidor St., National Science Complex, 1101, Quezon City, Philippines.

Recent data show a global increase in colorectal cancer (CRC) cases among younger demographics, which portends poorer prognosis. The cause of rising incidence is uncertain, and its mutational landscape remains largely unexplored, including those in genes of the epidermal growth factor receptor pathway. Among these are NRAS mutants where there is paucity of functional studies compared to KRAS. Read More

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http://dx.doi.org/10.1038/s41598-020-67796-8DOI Listing

Predicting and affecting response to cancer therapy based on pathway-level biomarkers.

Nat Commun 2020 Jul 3;11(1):3296. Epub 2020 Jul 3.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. Read More

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http://dx.doi.org/10.1038/s41467-020-17090-yDOI Listing

Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth.

Nat Commun 2020 Jul 3;11(1):3326. Epub 2020 Jul 3.

Department of Molecular Biology and Biochemistry; School of Biological Sciences, University of California, Irvine, Irvine, CA, 92697, USA.

Tumour cells adapt to nutrient deprivation in vivo, yet strategies targeting the nutrient poor microenvironment remain unexplored. In melanoma, tumour cells often experience low glutamine levels, which promote cell dedifferentiation. Here, we show that dietary glutamine supplementation significantly inhibits melanoma tumour growth, prolongs survival in a transgenic melanoma mouse model, and increases sensitivity to a BRAF inhibitor. Read More

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http://dx.doi.org/10.1038/s41467-020-17181-wDOI Listing

Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patients.

Cell Mol Immunol 2020 Jul 3. Epub 2020 Jul 3.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.

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http://dx.doi.org/10.1038/s41423-020-0492-xDOI Listing