263,774 results match your criteria Cancer Biology & Therapy [Journal]


Twisting the bone marrow stem cell niche.

Haematologica 2018 Dec 30;103(12):1937-1939. Epub 2018 Nov 30.

Division of Experimental Hematology and Cancer Biology, Cancer & Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati.

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http://dx.doi.org/10.3324/haematol.2018.206029DOI Listing
December 2018

Middle-way flexible docking: Pose prediction using mixed-resolution Monte Carlo in estrogen receptor α.

PLoS One 2019 23;14(4):e0215694. Epub 2019 Apr 23.

Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239, United States of America.

There is a vast gulf between the two primary strategies for simulating protein-ligand interactions. Docking methods significantly limit or eliminate protein flexibility to gain great speed at the price of uncontrolled inaccuracy, whereas fully flexible atomistic molecular dynamics simulations are expensive and often suffer from limited sampling. We have developed a flexible docking approach geared especially for highly flexible or poorly resolved targets based on mixed-resolution Monte Carlo (MRMC), which is intended to offer a balance among speed, protein flexibility, and sampling power. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215694PLOS
April 2019
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Structural and functional characterization of β -glycoprotein I domain 1 in anti-melanoma cell migration.

Cancer Sci 2019 Apr 23. Epub 2019 Apr 23.

Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.

We previously found that circulating β -glycoprotein I inhibits human endothelial cell migration, proliferation, and angiogenesis via diverse mechanisms. In the present study, we investigated the antitumor activities of β -glycoprotein I using structure-function analysis and mapped the critical region within the β -glycoprotein I peptide sequence that mediates anticancer effects. We constructed recombinant cDNA and purified different β -glycoprotein I polypeptide domains using a baculovirus expression system. Read More

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http://dx.doi.org/10.1111/cas.14030DOI Listing

Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53-altered tumors.

Cancer 2019 Apr 23. Epub 2019 Apr 23.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.

Background: Over 96% of high-grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.32053
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http://dx.doi.org/10.1002/cncr.32053DOI Listing
April 2019
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Fertility-related experiences after breast cancer diagnosis in the Sister and Two Sister Studies.

Cancer 2019 Apr 23. Epub 2019 Apr 23.

Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability.

Methods: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.32126
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http://dx.doi.org/10.1002/cncr.32126DOI Listing
April 2019
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Synthesis and antiproliferative activity of novel (+)- usnic acid analogues.

J Asian Nat Prod Res 2019 Apr 23:1-16. Epub 2019 Apr 23.

b Applied Biology Department , CSIR-Indian Institute of Chemical Technology , Hyderabad 500007 , India.

Twenty one novel (+)- usnic acid-based analogues belonging to three classes such as enamines, imines, and pyrazoles were synthesized. All the synthesized compounds were characterized by their spectral data (H NMR, C NMR, IR, and HRMS). The synthesized compounds were evaluated for their antiproliferative activity against a panel of four human cancer cell lines including HeLa (cervix), MDA-MB-231 (breast), A549 (lung), and MiaPaca (pancreas) by employing SRB cell proliferation assay. Read More

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http://dx.doi.org/10.1080/10286020.2019.1603220DOI Listing

The significance of tumor budding in oral cancer survival and its relevance to the eighth edition of the American Joint Committee on Cancer staging system.

Head Neck 2019 Apr 23. Epub 2019 Apr 23.

Department of Stomatology, Oral & Maxillofacial Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: To explore the clinicopathological significance of tumor budding (TB) on oral squamous cell carcinoma (OSCC) prognosis.

Methods: Data of 200 patients with OSCC were retrieved from the cancer registration database in Taipei Veterans General Hospital. Clinicopathological characteristics and survival relevant to TB were analyzed. Read More

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http://dx.doi.org/10.1002/hed.25780DOI Listing

3D Bioprinting in Skeletal Muscle Tissue Engineering.

Small 2019 Apr 23:e1805530. Epub 2019 Apr 23.

Center for Minimally Invasive Therapeutics (C-MIT), Department of Radiological Sciences, University of California, Los Angeles, CA, 90095, USA.

Skeletal muscle tissue engineering (SMTE) aims at repairing defective skeletal muscles. Until now, numerous developments are made in SMTE; however, it is still challenging to recapitulate the complexity of muscles with current methods of fabrication. Here, after a brief description of the anatomy of skeletal muscle and a short state-of-the-art on developments made in SMTE with "conventional methods," the use of 3D bioprinting as a new tool for SMTE is in focus. Read More

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http://dx.doi.org/10.1002/smll.201805530DOI Listing

IRF4 translocation status in pediatric follicular and diffuse large B-cell lymphoma patients enrolled in Children's Oncology Group trials.

Pediatr Blood Cancer 2019 Apr 22:e27770. Epub 2019 Apr 22.

Department of Pathology, University of Utah, Salt Lake City, Utah.

Large B-cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. In order to characterize these lymphomas in children from the United States, IRF4 FISH and immunohistochemical stains were performed on 32 follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) from Children's Oncology Group studies. Two DLBCLs (6%) had IRF4 rearrangements, one involving the ileocecal valve and another involving the tonsil and cerebrospinal fluid. Read More

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http://dx.doi.org/10.1002/pbc.27770DOI Listing
April 2019
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Cancer immunotherapy: advances and future challenges.

Immunol Cell Biol 2019 Apr;97(4):353-354

Department of Biochemistry and Molecular Biology, The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute, Parkville, VIC, 3010, Australia.

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http://dx.doi.org/10.1111/imcb.12250DOI Listing

Spatial control of oxygen delivery to three-dimensional cultures alters cancer cell growth and gene expression.

J Cell Physiol 2019 Apr 22. Epub 2019 Apr 22.

Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Commonly used monolayer cancer cell cultures fail to provide a physiologically relevant environment in terms of oxygen delivery. Here, we describe a three-dimensional (3D) bioreactor system where cancer cells are grown in Matrigel in modified six-well plates. Oxygen is delivered to the cultures through a polydimethylsiloxane (PDMS) membrane at the bottom of the wells, with microfabricated PDMS pillars to control oxygen delivery. Read More

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http://dx.doi.org/10.1002/jcp.28665DOI Listing

Comparing long-term local recurrence rates of surgical and non-surgical management of close anterior margins in breast conserving surgery.

Breast Cancer Res Treat 2019 Apr 22. Epub 2019 Apr 22.

Nightingale Breast Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Southmoor Road, Manchester, M23 9LT, UK.

Purpose: While it is known that histologically involved margins lead to a higher local recurrence rate, re-excision of anterior margins is less common than that of radial margins. However, there are minimal long-term data on the oncological safety of non-surgical management of anterior margins.

Patients And Methods: A retrospective study was performed of all patients who underwent breast conserving surgery for breast cancer between 2000 and 2008 at two tertiary referral centres. Read More

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http://dx.doi.org/10.1007/s10549-019-05242-8DOI Listing

Oncogene c-MYC Controls the Expression of PHF10 Subunit of PBAF Chromatin Remodeling Complex in SW620 Cell Line.

Dokl Biochem Biophys 2019 May 22;484(1):66-68. Epub 2019 Apr 22.

Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia.

The PBAF(SWI/SNF) multiprotein complex, which changes the chromatin structure, is widely involved in the regulation of eukaryotic gene expression. A specific component of this complex is the PHF10 protein, which is involved in recruiting this complex to chromatin. We showed that the PHF10 expression in cells of different lines is activated by the c-MYC oncogene. Read More

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http://dx.doi.org/10.1134/S1607672919010204DOI Listing

High-grade glioneuronal tumor with an ARHGEF2-NTRK1 fusion gene.

Brain Tumor Pathol 2019 Apr 22. Epub 2019 Apr 22.

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

Here, we report a highly unusual case of high-grade glioneuronal tumor with a neurotrophic tropomyosin receptor kinase (NTRK) fusion gene. A 13-year-old girl presented with headache and vomiting and MRI detected two cystic lesions bilaterally in the frontal areas with surrounding edema. The left larger tumor was removed by left frontal craniotomy. Read More

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http://dx.doi.org/10.1007/s10014-019-00345-yDOI Listing

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

Int J Clin Oncol 2019 Apr 22. Epub 2019 Apr 22.

Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

n the original publication, in a title of Table 2. Read More

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http://link.springer.com/10.1007/s10147-019-01444-8
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http://dx.doi.org/10.1007/s10147-019-01444-8DOI Listing
April 2019
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Identifying Potential Prognostic Markers for Muscle-Invasive Bladder Urothelial Carcinoma by Weighted Gene Co-Expression Network Analysis.

Pathol Oncol Res 2019 Apr 22. Epub 2019 Apr 22.

Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, 215123, China.

Muscle-invasive bladder urothelial carcinoma (MIBC) is characterized as a genetic heterogeneous cancer with a high percentage of recurrence and worse prognosis. Identify the prognostic potentials of novel genes for muscle-invasive urothelial bladder cancer could at least provide important information for early detection and clinical treatment. Weighted gene co-expression network analysis (WGCNA) algorithm, a powerful systems biology approach, was utilized to extract co-expressed gene networks from mRNA expression dataset to construct transcriptional modules in MIBC samples, which was associated with demographic and clinical traits of MIBC patients. Read More

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http://dx.doi.org/10.1007/s12253-019-00657-6DOI Listing

SN-38, the active metabolite of irinotecan, inhibits the acute inflammatory response by targeting toll-like receptor 4.

Cancer Chemother Pharmacol 2019 Apr 22. Epub 2019 Apr 22.

Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceará, Rua Cel Nunes de Melo, 1127, Rodolfo Teófilo, Fortaleza, Ceará, 60430-270, Brazil.

Purpose: Anticancer-drug efficacy seems to involve the direct interaction with host immune cells. Although topoisomerase I (Top I) inhibitors have been suggested to block LPS-evoked inflammation, the interaction between these drugs and toll-like receptor 4 (TLR4) is unaddressed.

Methods: SN-38, the active metabolite of the Top I inhibitor irinotecan, and TLR4 interaction was assessed using the in vitro luciferase nuclear factor-κB reporter assay, neutrophil migration to murine air-pouch, in silico simulation, and the thermal shift assay (TSA). Read More

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http://dx.doi.org/10.1007/s00280-019-03844-zDOI Listing

Reactivity of Cu(ii)-, Zn(ii)- and Fe(ii)-thiosemicarbazone complexes with glutathione and metallothionein: from stability to dissociation to transmetallation.

Metallomics 2019 Apr 23. Epub 2019 Apr 23.

Institut de Chimie, UMR 7177, CNRS-Université de Strasbourg, 4 rue Blaise Pascal, 67000, Strasbourg, France. and University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg, France.

Thiosemicarbazones (TSCs) are a class of strong metal ion ligands, which are currently being investigated for several applications, such as anticancer treatment. In addition to these ligands only, which exert their activity upon interaction with metal ions in cells, preformed metal-TSC complexes are also widely studied, predominantly with the essential metal ions iron, copper and zinc. Currently, it is unclear what the active species are, which complexes are present and what are their biological targets. Read More

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http://dx.doi.org/10.1039/c9mt00061eDOI Listing
April 2019
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Fibrinogen and fibrin: An illustrated review.

Res Pract Thromb Haemost 2019 Apr 4;3(2):161-172. Epub 2019 Mar 4.

Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill North Carolina.

Since its discovery over 350 years ago, studies of fibrinogen have revealed remarkable characteristics. Its complex structure as a large (340 kDa) hexameric homodimer supports complex roles in hemostasis and homeostasis. Fibrinogen synthesis is regulated at the transcriptional and translational levels, undergoing both constitutive (basal) secretion from liver, and inducible upregulation in response to inflammatory events. Read More

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http://doi.wiley.com/10.1002/rth2.12191
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http://dx.doi.org/10.1002/rth2.12191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462751PMC
April 2019
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Applications of ENCODE data to Systematic Analyses via Data Integration.

Curr Opin Syst Biol 2018 Oct 29;11:57-64. Epub 2018 Aug 29.

Department of Biomedical Data Science, The Geisel School of Medicine at Dartmouth College, One Medical Center Dr., Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States, 03756.

Large-scale genomic data have been utilized to generate unprecedented biological findings and new hypotheses. To delineate functional elements in the human genome, the Encyclopedia of DNA Elements (ENCODE) project has generated an enormous amount of genomic data, yielding around 7,000 data profiles in different cell and tissue types. In this article, we reviewed the systematic analyses that have integrated ENCODE data with other data sources to reveal new biological insights, ranging from human genome annotation to the identification of new candidate drugs. Read More

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http://dx.doi.org/10.1016/j.coisb.2018.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474416PMC
October 2018

Increases in Serial Pretreatment F-FDG PET-CT Metrics Predict Survival in Early Stage Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy.

Adv Radiat Oncol 2019 Apr-Jun;4(2):429-437. Epub 2018 Nov 26.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.

Purpose: Quantitative changes in positron emission tomography with computed tomography imaging metrics over serial scans may be predictive biomarkers. We evaluated the relationship of pretreatment metabolic tumor growth rate (MTGR) and standardized uptake value velocity (SUVV) with disease recurrence or death in patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy (SABR).

Methods And Materials: Under institutional review board approval, we retrospectively identified patients who underwent positron emission tomography with computed tomography at diagnosis and staging and simulation for SABR. Read More

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http://dx.doi.org/10.1016/j.adro.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460103PMC
November 2018

Evaluation of oxidative stress and the microenvironment in oral submucous fibrosis.

Heliyon 2019 Apr 12;5(4):e01502. Epub 2019 Apr 12.

School of Medical Science and Technology, IIT Kharagpur, India.

Background: Oral Submucous fibrosis (OSF) is a chronic inflammatory mucosal disease of unknown etiology. Statistics show cases of OSF which has a high rate of overall prevalence and increase the chance of malignant transformation. As we know malignant cells is situated in a very complex microenvironment with altered metabolic pathway including intermediates which participate in oxidative stress process which enhances metabolic rewiring and promotes tumor progression. Read More

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http://dx.doi.org/10.1016/j.heliyon.2019.e01502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462775PMC

Discretionary Transduction of MMP-Sensitized Tousled in Head and Neck Cancer.

Mol Ther Oncolytics 2019 Sep 20;14:57-65. Epub 2019 Mar 20.

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.

Oral radiotoxicity is often a limiting factor in cancer treatment. Previously, we demonstrated that transfer of cell-permeable, TAT-fusion Tousled-like kinase 1B (TLK1B) protein in salivary glands effectively mitigates radiation-induced salivary dysfunction. However, similar to most radioprotectors, TLK1B can carry the risk of limiting cancer treatment efficacy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23727705193001
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http://dx.doi.org/10.1016/j.omto.2019.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463741PMC
September 2019
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Mouse germ line mutations due to retrotransposon insertions.

Mob DNA 2019 13;10:15. Epub 2019 Apr 13.

1Terry Fox Laboratory, BC Cancer and Department of Medical Genetics, University of British Columbia, V5Z1L3, Vancouver, BC Canada.

Transposable element (TE) insertions are responsible for a significant fraction of spontaneous germ line mutations reported in inbred mouse strains. This major contribution of TEs to the mutational landscape in mouse contrasts with the situation in human, where their relative contribution as germ line insertional mutagens is much lower. In this focussed review, we provide comprehensive lists of TE-induced mouse mutations, discuss the different TE types involved in these insertional mutations and elaborate on particularly interesting cases. Read More

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http://dx.doi.org/10.1186/s13100-019-0157-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466679PMC

Quantitative proteomic analysis of prostate tissue specimens identifies deregulated protein complexes in primary prostate cancer.

Clin Proteomics 2019 13;16:15. Epub 2019 Apr 13.

Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Rm. 4009, Davis Research Bldg 8700 Beverly Blvd, Los Angeles, CA 90048 USA.

Background: Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and a leading cause of mortality among males in developed countries. However, our understanding of the global changes of protein complexes within PCa tissue specimens remains very limited, although it has been well recognized that protein complexes carry out essentially all major processes in living organisms and that their deregulation drives the pathogenesis and progression of various diseases.

Methods: By coupling tandem mass tagging-synchronous precursor selection-mass spectrometry/mass spectrometry/mass spectrometry with differential expression and co-regulation analyses, the present study compared the differences between protein complexes in normal prostate, low-grade PCa, and high-grade PCa tissue specimens. Read More

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http://dx.doi.org/10.1186/s12014-019-9236-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461817PMC

OTU deubiquitinase 4 is silenced and radiosensitizes non-small cell lung cancer cells via inhibiting DNA repair.

Cancer Cell Int 2019 15;19:99. Epub 2019 Apr 15.

3Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Tianjin Medical University, Tianjin, 300070 China.

Background: Radiotherapy is becoming one major therapeutics for non-small cell lung cancer (NSCLC). Identifying novel radiosensitizers will greatly increase the efficacy of radiotherapy and benefit more patients. OTU deubiquitinase 4 (OTUD4) has been reported involved in DNA damage repair pathways and could be a potential target for chemotherapy therapy. Read More

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http://dx.doi.org/10.1186/s12935-019-0816-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466656PMC

Reply to 'Comment on "Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysis"'.

Br J Cancer 2019 Apr 23. Epub 2019 Apr 23.

Department of Medical Biology, Faculty of Health Sciences, University of Tromsø - The Arctic University of Norway, 9037, Tromsø, Norway.

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http://dx.doi.org/10.1038/s41416-019-0460-3DOI Listing

Immunogenic neoantigens derived from gene fusions stimulate T cell responses.

Nat Med 2019 Apr 22. Epub 2019 Apr 22.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. Read More

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http://dx.doi.org/10.1038/s41591-019-0434-2DOI Listing

Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study.

Nat Med 2019 Apr 22. Epub 2019 Apr 22.

Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UK.

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. Read More

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http://dx.doi.org/10.1038/s41591-019-0380-zDOI Listing

Synthetic gene circuits for the detection, elimination and prevention of disease.

Nat Biomed Eng 2018 Jun 11;2(6):399-415. Epub 2018 Jun 11.

Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.

In living organisms, naturally evolved sensors that constantly monitor and process environmental cues trigger corrective actions that enable the organisms to cope with changing conditions. Such natural processes have inspired biologists to construct synthetic living sensors and signalling pathways, by repurposing naturally occurring proteins and by designing molecular building blocks de novo, for customized diagnostics and therapeutics. In particular, designer cells that employ user-defined synthetic gene circuits to survey disease biomarkers and to autonomously re-adjust unbalanced pathological states can coordinate the production of therapeutics, with controlled timing and dosage. Read More

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http://www.nature.com/articles/s41551-018-0215-0
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http://dx.doi.org/10.1038/s41551-018-0215-0DOI Listing
June 2018
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Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells.

Nat Methods 2019 Apr 22. Epub 2019 Apr 22.

Technology Innovation Laboratory, New York Genome Center, New York, NY, USA.

Multimodal single-cell assays provide high-resolution snapshots of complex cell populations, but are mostly limited to transcriptome plus an additional modality. Here, we describe expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq) for the high-throughput characterization of at least five modalities of information from each single cell. We demonstrate application of ECCITE-seq to multimodal CRISPR screens with robust direct single-guide RNA capture and to clonotype-aware multimodal phenotyping of cancer samples. Read More

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http://www.nature.com/articles/s41592-019-0392-0
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http://dx.doi.org/10.1038/s41592-019-0392-0DOI Listing
April 2019
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U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies.

Nat Cell Biol 2019 Apr 22. Epub 2019 Apr 22.

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Spliceosome mutations are common in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), but the oncogenic changes due to these mutations have not been identified. Here a global analysis of exon usage in AML samples revealed distinct molecular subsets containing alternative spliced isoforms of inflammatory and immune genes. Interleukin-1 receptor-associated kinase 4 (IRAK4) was the dominant alternatively spliced isoform in MDS and AML and is characterized by a longer isoform that retains exon 4, which encodes IRAK4-long (IRAK4-L), a protein that assembles with the myddosome, results in maximal activation of nuclear factor kappa-light-chain-enhancer of B cells (NF-κB) and is essential for leukaemic cell function. Read More

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http://dx.doi.org/10.1038/s41556-019-0314-5DOI Listing

Monoclonal gammopathy of undetermined significance (MGUS).

Blood 2019 Apr 22. Epub 2019 Apr 22.

Medical Oncology/Hematologic Malignancies, Dana-Farber Cancer Institute, United States

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of progression per year. Recent advances have improved understanding of the complex genetic and immunologic factors that drive and permit progression from aberrant plasma cell clone to MGUS and overt MM. Additional evidence supports a bidirectional interaction of MGUS cells with surrounding cells in the bone marrow niche that regulates malignant transformation. Read More

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http://dx.doi.org/10.1182/blood.2019846782DOI Listing

A novel orally active inverse agonist of estrogen-related receptor gamma (ERRγ), DN200434, a booster of NIS in anaplastic thyroid cancer.

Clin Cancer Res 2019 Apr 22. Epub 2019 Apr 22.

Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation

Purpose: New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy-refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERRγ) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC = 0. Read More

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http://dx.doi.org/10.1158/1078-0432.CCR-18-3007DOI Listing

Novel RB1-loss transcriptomic signature is associated with poor clinical outcomes across cancer types.

Clin Cancer Res 2019 Apr 22. Epub 2019 Apr 22.

Radiation Oncology, Helen Diller Comprehensive Cancer Center, University of California, San Francisco

Purpose: Rb-pathway disruption is of great clinical interest, as it has been shown to predict outcomes in multiple cancers. We sought to develop a transcriptomic signature for detecting bi-allelic loss (RBS) that could be used to assess the clinical implications of loss on a pan-cancer scale.

Experimental Design: We utilized data from the Cancer Cell Line Encyclopedia (N=995) to develop the first pan-cancer transcriptomic signature for predicting bi-allelic loss (RBS). Read More

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http://dx.doi.org/10.1158/1078-0432.CCR-19-0404DOI Listing

Production of a Functional Factor, p40, by GG Is Promoted by Intestinal Epithelial Cell-secreted Extracellular Vesicles.

Infect Immun 2019 Apr 22. Epub 2019 Apr 22.

Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt; University Medical Center, Nashville, TN, 37232, USA

The symbiotic relationship between the gut microbiome and the host provides a nutrient-rich environment for gut microbes and has beneficial effects on host health. Although the composition of the gut microbiome is known to be influenced by both host genetics and environmental factors, host effects on the activities and functions of the gut microbial communities remain poorly understood. Intestinal epithelial cells exert front-line responses to gut microbes and contribute to maintaining a healthy intestinal homeostasis. Read More

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http://dx.doi.org/10.1128/IAI.00113-19DOI Listing

Diversification and evolution of vancomycin-resistant during intestinal domination.

Infect Immun 2019 Apr 22. Epub 2019 Apr 22.

Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center

Vancomycin-resistant (VRE) is a leading cause of hospital-acquired infections. This is particularly true in immunocompromised patients where the damage to the microbiota caused by antibiotics can lead to VRE domination of the intestine, increasing a patient's risk for bloodstream infection. In previous studies we observed that the intestinal domination by VRE of patients hospitalized to receive allogeneic bone marrow transplantation can persist for weeks, but little is known about sub-species diversification and evolution during prolonged domination. Read More

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http://dx.doi.org/10.1128/IAI.00102-19DOI Listing

An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses.

Radiother Oncol 2019 Apr 19. Epub 2019 Apr 19.

Department of Radiation Oncology, University of California, Irvine, United States.

For decades the field of radiation oncology has sought to improve the therapeutic ratio through innovations in physics, chemistry, and biology. To date, technological advancements in image guided beam delivery techniques have provided clinicians with their best options for improving this critical tool in cancer care. Medical physics has focused on the preferential targeting of tumors while minimizing the collateral dose to the surrounding normal tissues, yielding only incremental progress. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01678140193015
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http://dx.doi.org/10.1016/j.radonc.2019.03.028DOI Listing
April 2019
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Oligonucleotide-directed STAT3 alternative splicing switch drives anti-tumorigenic outcomes in MCF10 human breast cancer cells.

Biochem Biophys Res Commun 2019 Apr 19. Epub 2019 Apr 19.

Department of Biochemistry and Molecular Biology, Medical Building, University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address:

Signal transducer and activator of transcription 3 (STAT3), a transcription factor responsive to the activation of cytokine receptors, is known for its oncogenic actions. Whilst STAT3α is the predominant spliceform in most tissues, alternative splicing of the STAT3 gene can generate a shorter STAT3β spliceform. Redirecting splicing to enhance STAT3β levels can result in tumor suppression in vivo, and so we evaluated the cellular basis underlying the anti-tumorigenic properties of STAT3β. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0006291X193068
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http://dx.doi.org/10.1016/j.bbrc.2019.04.054DOI Listing
April 2019
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A novel antibody-drug conjugate, HcHAb18-DM1, has potent anti-tumor activity against human non-small cell lung cancer.

Biochem Biophys Res Commun 2019 Apr 19. Epub 2019 Apr 19.

National Translational Science Center for Molecular Medicine, Air Force Medical University, Xi'an, 710032, China; Department of Cell Biology, School of Basic Medicine, Air Force Medical University, Xi'an, 710032, China. Electronic address:

Cluster of differentiation 147 (CD147), a transmembrane protein of the immunoglobulin superfamily, is a potential target of treatment against human non-small cell lung cancer (NSCLC). Although there have been exciting advances in epidermal growth factor receptor (EGFR)-targeted therapy for NSCLC in recent years, additional novel targeted agents are needed to improve the efficiency and to offer more options for patients. Antibody-drug conjugates (ADCs) utilize a chemical linker to conjugate cytotoxic drugs to a monoclonal antibody to maximize the delivery to target cells and minimize the delivery to other normal cells. Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.04.046DOI Listing

Separating the Dreadful from the Merely Bad: Towards Prognostic and Predictive Biomarkers in Metastatic Castration-resistant Prostate Cancer.

Authors:
Michael Fraser

Eur Urol 2019 Apr 19. Epub 2019 Apr 19.

Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2019.04.005DOI Listing

The MTORC1-mediated autophagy is regulated by the FBXW7-SHOC2-RPTOR axis.

Autophagy 2019 Apr 22. Epub 2019 Apr 22.

b Division of Radiation and Cancer Biology, Department of Radiation Oncology , University of Michigan , Ann Arbor , MI 48109 , USA .

MTORC1 is a well-known key regulator of macroautophagy/autophagy. However, the underlying regulatory mechanisms of MTORC1 activity remains elusive. We showed recently that SHOC2, a RAS activator, competes with MTOR for RPTOR (but not RICTOR) binding, leading to MTORC1 inactivation, autophagy induction and cell survival, whereas RPTOR competes with RAS for SHOC2 binding to inactivate RAS-MAPK and suppresses growth. Read More

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http://dx.doi.org/10.1080/15548627.2019.1609864DOI Listing

Decreased ADAMTS-1, -9 and -20 levels in women with endometrial polyps: a possible link between extracellular matrix proteases and endometrial pathologies.

J Obstet Gynaecol 2019 Apr 22:1-6. Epub 2019 Apr 22.

b Department of Clinical Biochemistry , Ankara Numune Training and Research Hospital University of Health Sciences , Ankara , Turkey.

A disintegrin-like and metalloproteinase domain with thrombospondin-type 1 motifs (ADAMTS) protein superfamily includes 19 secreted metalloproteases. Proteolytic substrates of ADAMTS enzymes have been linked to female reproductive function. Herein, we aimed to investigate serum ADAMTS-1, -9 and -20 levels in women with and without endometrial polyps (EPs). Read More

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http://dx.doi.org/10.1080/01443615.2019.1584890DOI Listing

Influence of the HDAC Inhibitor Valproic Acid on the Growth and Proliferation of Temsirolimus-Resistant Prostate Cancer Cells In Vitro.

Cancers (Basel) 2019 Apr 19;11(4). Epub 2019 Apr 19.

Department of Urology, Goethe-University, D-60590 Frankfurt am Main, Germany.

The mechanistic target of rapamycin (mTOR) is elevated in prostate cancer, making this protein attractive for tumor treatment. Unfortunately, resistance towards mTOR inhibitors develops and the tumor becomes reactivated. We determined whether epigenetic modulation by the histone deacetylase (HDAC) inhibitor, valproic acid (VPA), may counteract non-responsiveness to the mTOR inhibitor, temsirolimus, in prostate cancer (PCa) cells. Read More

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http://dx.doi.org/10.3390/cancers11040566DOI Listing

Feline Foamy Virus is Highly Prevalent in Free-Ranging from Colorado, Florida and Southern California.

Viruses 2019 Apr 19;11(4). Epub 2019 Apr 19.

Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.

Feline foamy virus (FFV) is a retrovirus that has been detected in multiple feline species, including domestic cats () and pumas (). FFV results in persistent infection but is generally thought to be apathogenic. Sero-prevalence in domestic cat populations has been documented in several countries, but the extent of viral infections in nondomestic felids has not been reported. Read More

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https://www.mdpi.com/1999-4915/11/4/359
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http://dx.doi.org/10.3390/v11040359DOI Listing
April 2019
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The Antioxidant from Ethanolic Extract of Fruits Activates Phosphatase and Tensin Homolog In Vitro and In Vivo: A New Insight on Its Antileukemic Effect.

Int J Mol Sci 2019 Apr 19;20(8). Epub 2019 Apr 19.

Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan.

Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of fruits (RCE) along with its underlying mechanism of action. Read More

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http://dx.doi.org/10.3390/ijms20081935DOI Listing

Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas.

Cells 2019 Apr 21;8(4). Epub 2019 Apr 21.

Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary Street, 61-866 Poznan, Poland.

Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Read More

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http://dx.doi.org/10.3390/cells8040366DOI Listing

MSC.sTRAIL Has Better Efficacy than MSC.FL-TRAIL and in Combination with AKTi Blocks Pro-Metastatic Cytokine Production in Prostate Cancer Cells.

Cancers (Basel) 2019 Apr 21;11(4). Epub 2019 Apr 21.

Cancer and Stem Cell Biology Group, School of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK.

Cell therapy is a promising new treatment option for cancer. In particular, mesenchymal stem cells (MSCs) have shown potential in delivering therapeutic genes in various tumour models and are now on the verge of being tested in the clinic. A number of therapeutic genes have been examined in this context, including the death ligand TRAIL. Read More

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http://dx.doi.org/10.3390/cancers11040568DOI Listing

Metastatic Niches and the Modulatory Contribution of Mesenchymal Stem Cells and Its Exosomes.

Int J Mol Sci 2019 Apr 20;20(8). Epub 2019 Apr 20.

Remodelative Processes and Cellular Niches Laboratory, Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB)-CONICET-Instituto Universitario del Hospital Italiano-Hospital Italiano Buenos Aires (HIBA), C1199ACL Buenos Aires, Argentina.

Mesenchymal stem cells (MSCs) represent an interesting population due to their capacity to release a variety of cytokines, chemokines, and growth factors, and due to their motile nature and homing ability. MSCs can be isolated from different sources, like adipose tissue or bone marrow, and have the capacity to differentiate, both in vivo and in vitro, into adipocytes, chondrocytes, and osteoblasts, making them even more interesting in the regenerative medicine field. Tumor associated stroma has been recognized as a key element in tumor progression, necessary for the biological success of the tumor, and MSCs represent a functionally fundamental part of this associated stroma. Read More

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http://dx.doi.org/10.3390/ijms20081946DOI Listing

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - Endorsed by the European Academy of Neurology.

Eur Stroke J 2017 Sep 21;2(3):195-221. Epub 2017 Jul 21.

Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands.

The current proposal for cerebral venous thrombosis guideline followed the Grading of Recommendations, Assessment, Development, and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews of all available evidence and writing recommendations and deciding on their strength on an explicit and transparent manner, based on the quality of available scientific evidence. The guideline addresses both diagnostic and therapeutic topics. We suggest using magnetic resonance or computed tomography angiography for confirming the diagnosis of cerebral venous thrombosis and not screening patients with cerebral venous thrombosis routinely for thrombophilia or cancer. Read More

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http://journals.sagepub.com/doi/10.1177/2396987317719364
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http://dx.doi.org/10.1177/2396987317719364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454824PMC
September 2017
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