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https://www.readbyqxmd.com/read/29777994/analysis-of-incidence-mortality-and-survival-for-pancreatic-and-biliary-tract-cancers-across-europe-with-assessment-of-influence-of-revised-european-age-standardisation-on-estimates
#1
Pamela Minicozzi, Tiziana Cassetti, Claudia Vener, Milena Sant
BACKGROUND: Pancreatic (PC) and biliary tract (BTC) cancers have higher incidence and mortality in Europe than elsewhere. We analysed time-trends in PC/BTC incidence, mortality, and survival across Europe. Since the European standard population (ESP) was recently revised to better represent European age structure, we also assessed the effect of adopting the revised ESP to age-standardise incidence and mortality data. METHODS: We analysed PCs/BTCs (≥15 years) diagnosed in 2000-2007 and followed-up to end of 2008, in 29 European countries across five regions: UK/Ireland, and northern, central, southern, and eastern Europe...
May 16, 2018: Cancer Epidemiology
https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#2
Oliver A Zill, Kimberly C Banks, Stephen R Fairclough, Stefanie Mortimer, James V Vowles, Reza Mokhtari, David R Gandara, Philip C Mack, Justin I Odegaard, Rebecca J Nagy, Arthur M Baca, Helmy Eltoukhy, Darya I Chudova, Richard B Lanman, AmirAli Talasaz
PURPOSE: Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29776632/molecular-diagnosis-of-hematopoietic-neoplasms-2018-update
#3
REVIEW
Radhakrishnan Ramchandren, Tarek Jazaerly, Martin H Bluth, Ali M Gabali
Diagnosis of hematologic malignancies have matured to encompass molecular as well as phenotypic characteristics. Cytogenetic abnormalities are considered common events in this regard. These abnormalities generally consist of structural chromosomal abnormalities or gene mutations, which often are integral to the pathogenesis and subsequent evolution of an individual malignancy. Improvements made in identifying and interpreting these molecular alterations have resulted in advances in the diagnosis, prognosis, monitoring, and therapy for cancer...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#4
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772748/drug-delivery-strategies-for-antivirals-against-hepatitis-b-virus
#5
REVIEW
Latavia Singh, Sunaina Indermun, Mershen Govender, Pradeep Kumar, Lisa C du Toit, Yahya E Choonara, Viness Pillay
Chronic hepatitis B virus (HBV) infection poses a significant health challenge due to associated morbidity and mortality from cirrhosis and hepatocellular cancer that eventually results in the breakdown of liver functionality. Nanotechnology has the potential to play a pivotal role in reducing viral load levels and drug-resistant HBV through drug targeting, thus reducing the rate of evolution of the disease. Apart from tissue targeting, intracellular delivery of a wide range of drugs is necessary to exert a therapeutic action in the affected organelles...
May 17, 2018: Viruses
https://www.readbyqxmd.com/read/29771315/palimpsest-an-r-package-for-studying-mutational-and-structural-variant-signatures-along-clonal-evolution-in-cancer
#6
Jayendra Shinde, Quentin Bayard, Sandrine Imbeaud, Théo Z Hirsch, Feng Liu, Victor Renault, Jessica Zucman-Rossi, Eric Letouzé
Summary: Cancer genomes are altered by various mutational processes and, like palimpsests, bear the signatures of these different processes. The Palimpsest R package provides a complete workflow for the characterization and visualization of mutational signatures and their evolution along tumor development. The package covers a wide range of functions for extracting both base substitution and structural variant signatures, inferring the clonality of each alteration and analyzing the evolution of mutational processes between early clonal and late subclonal events...
May 16, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29770900/insights-into-mutation-effect-in-three-poikiloderma-with-neutropenia-patients-by-transcript-analysis-and-disease-evolution-of-reported-patients-with-the-same-pathogenic-variants
#7
Elisa A Colombo, Nursel H Elcioglu, Claudio Graziano, Pamela Farinelli, Elisabetta Di Fede, Iria Neri, Elena Facchini, Mariangela Greco, Cristina Gervasini, Lidia Larizza
PURPOSE: Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients...
May 16, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29769386/global-acceptance-of-biosimilars-importance-of-regulatory-consistency-education-and-trust
#8
REVIEW
Eduardo Cazap, Ira Jacobs, Ali McBride, Robert Popovian, Karol Sikora
Globally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29769258/anti-tumor-efficacy-of-a-novel-clk-inhibitor-via-targeting-rna-splicing-and-myc-dependent-vulnerability
#9
Kenichi Iwai, Masahiro Yaguchi, Kazuho Nishimura, Yukiko Yamamoto, Toshiya Tamura, Daisuke Nakata, Ryo Dairiki, Yoichi Kawakita, Ryo Mizojiri, Yoshiteru Ito, Moriteru Asano, Hironobu Maezaki, Yusuke Nakayama, Misato Kaishima, Kozo Hayashi, Mika Teratani, Shuichi Miyakawa, Misa Iwatani, Maki Miyamoto, Michael G Klein, Wes Lane, Gyorgy Snell, Richard Tjhen, Xingyue He, Sai Pulukuri, Toshiyuki Nomura
The modulation of pre-mRNA splicing is proposed as an attractive anti-neoplastic strategy, especially for the cancers that exhibit aberrant pre-mRNA splicing. Here, we discovered that T-025 functions as an orally available and potent inhibitor of Cdc2-like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T-025 reduced CLK-dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive-associated biomarker of T-025...
May 16, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29769134/advances-on-chimeric-antigen-receptor-modified-t-cell-therapy-for-oncotherapy
#10
REVIEW
Yanyu Pang, Xiaoyang Hou, Chunsheng Yang, Yanqun Liu, Guan Jiang
Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease...
May 16, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29765043/programmable-sequential-mutagenesis-by-inducible-cpf1-crrna-array-inversion
#11
Ryan D Chow, Hyunu Ray Kim, Sidi Chen
Mutations and genetic alterations are often sequentially acquired in various biological and pathological processes, such as development, evolution, and cancer. Certain phenotypes only manifest with precise temporal sequences of genetic events. While multiple approaches have been developed to model the effects of mutations in tumorigenesis, few recapitulate the stepwise nature of cancer evolution. Here we describe a flexible sequential mutagenesis system, Cpf1-Flip, with inducible inversion of a single crRNA array (FlipArray), and demonstrate its application in stepwise mutagenesis in murine and human cells...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764582/-research-advances-in-the-role-of-aptamers-in-the-diagnosis-and-targeted-therapy-of-pediatric-cancer
#12
Yi-Bin Zhang, Yan-Peng Wang, Jing Liu
Aptamers are single-stranded DNA or RNA which are isolated from synthesized random oligonucleotide library in vitro via systematic evolution of ligands by exponential enrichment (SELEX) and can bind to metal ions, small molecules, carbohydrates, lipids, proteins, and others targets with high affinity and specificity. Aptamers have the advantages of simple preparation, good thermal stability, and low immunogenicity and have great potential in the medical fields such as molecular imaging, biosensing, early diagnosis of diseases, and targeted therapy...
May 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29761881/expression-of-stem-cell-markers-nanog-and-nestin-in-lip-squamous-cell-carcinoma-and-actinic-cheilitis
#13
Fernanda M Scotti, Verônica C Mitt, Daniella S C Vieira, Michelle T Biz, Renata G Castro, Filipe Modolo
Cancer stem cells ( CSC ) proteins have been observed in several lesions and are associated with tumor beginning, evolution, and resistance to treatment. OBJECTIVES: to investigate the presence of NANOG, NESTIN, and β-tubulin in lip squamous cell carcinoma (LSCC), actinic cheilitis (AC), and normal epithelium (NE). MATERIALS AND METHODS: thirty cases of LSCC, thirty cases of AC (both analyzed according to the WHO classification and AC according to the binary classification), and twenty cases of NE were submitted to an immunohistochemical study...
May 15, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29760831/current-status-of-organ-preservation-in-carcinoma-larynx
#14
REVIEW
Tapesh Bhattacharyya, Cessal Thommachan Kainickal
Organ preservation in carcinoma larynx is a long debated topic. There are multiple organ preserving approaches in the management of carcinoma larynx depending on various factors. Radical radiotherapy (RT) and conservation laryngeal surgery have shown equivalent results in early laryngeal cancer. Concurrent chemoradiation (CTRT) is the standard treatment in stage III and IV laryngeal cancer with intact cartilage and functional larynx. Patients with cartilage destruction or dysfunctional larynx are not the candidates for organ preservation...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29760781/understanding-aneuploidy-in-cancer-through-the-lens-of-system-inheritance-fuzzy-inheritance-and-emergence-of-new-genome-systems
#15
REVIEW
Christine J Ye, Sarah Regan, Guo Liu, Sarah Alemara, Henry H Heng
Background: In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of how aneuploidy contributes to cancer becomes increasingly challenging: since aneuploidy can be linked to diverse molecular pathways (in regards to both cause and effect), the chances of it being cancerous is highly context-dependent, making it more difficult to study than individual molecular mechanisms...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29760738/dental-mesenchymal-stem-stromal-cells-and-their-exosomes
#16
REVIEW
Peter Stanko, Ursula Altanerova, Jana Jakubechova, Vanda Repiska, Cestmir Altaner
Stem cells derived from human dental pulp tissue (DP-MSC) differ from the other mesenchymal stem cells prepared from bone marrow or adipose tissue due to their embryonic origin from the neural crest and are of special interest because of their neurotropic character. Furthermore, the therapeutic potential of DP-MSCs is realized through paracrine action of extracellularly released components, for which exosomes play an important role. In this review, we intend to explore the properties of these cells with an emphasis on exosomes...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760052/spatial-mutation-patterns-as-markers-of-early-colorectal-tumor-cell-mobility
#17
Marc D Ryser, Byung-Hoon Min, Kimberly D Siegmund, Darryl Shibata
A growing body of evidence suggests that a subset of human cancers grows as single clonal expansions. In such a nearly neutral evolution scenario, it is possible to infer the early ancestral tree of a full-grown tumor. We hypothesized that early tree reconstruction can provide insights into the mobility phenotypes of tumor cells during their first few cell divisions. We explored this hypothesis by means of a computational multiscale model of tumor expansion incorporating the glandular structure of colorectal tumors...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29760044/nk-cells-mediate-synergistic-antitumor-effects-of-combined-inhibition-of-hdac6-and-bet-in-a-sclc-preclinical-model
#18
Yan Liu, Yuyang Li, Shengwu Liu, Dennis O Adeegbe, Camilla L Christensen, Max M Quinn, Ruben Dries, Shiwei Han, Kevin Buczkowski, Xiaoen Wang, Ting Chen, Peng Gao, Hua Zhang, Fei Li, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Small cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications in SCLC suggest that transcriptional and epigenetic regulations play a major role in SCLC disease evolution. Here we performed a synthetic lethal screen using the BET inhibitor JQ1 and an shRNA library targeting 550 epigenetic genes in treatment-refractory SCLC xenograft models and identified HDAC6 as a synthetic lethal target in combination with JQ1...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29757235/clinically-applicable-inhibitors-impacting-genome-stability
#19
REVIEW
Anu Prakash, Juan F Garcia-Moreno, James A L Brown, Emer Bourke
Advances in technology have facilitated the molecular profiling (genomic and transcriptomic) of tumours, and has led to improved stratification of patients and the individualisation of treatment regimes. To fully realize the potential of truly personalised treatment options, we need targeted therapies that precisely disrupt the compensatory pathways identified by profiling which allow tumours to survive or gain resistance to treatments. Here, we discuss recent advances in novel therapies that impact the genome (chromosomes and chromatin), pathways targeted and the stage of the pathways targeted...
May 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29756349/integrating-the-dna-damage-and-protein-stress-responses-during-cancer-development-and-treatment
#20
REVIEW
Vassilis G Gorgoulis, Dafni-Eleftheria Pefani, Ioannis S Pateras, Ioannis P Trougakos
Cells have developed during evolution a wide spectrum of stress response modules to assure homeostasis. The genome and proteome damage response pathways constitute the pillars of this interwoven "defensive" network. Consequently, the deregulation of these pathways correlates with aging and various pathophysiological states, including cancer. In the present review we highlight: i) the structure of the genome and proteome damage response pathways, ii) their functional crosstalk and, iii) the conditions under which they predispose to cancer...
May 13, 2018: Journal of Pathology
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