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https://www.readbyqxmd.com/read/27926867/genomic-instability-is-induced-by-persistent-proliferation-of-cells-undergoing-epithelial-to-mesenchymal-transition
#1
Valentine Comaills, Lilian Kabeche, Robert Morris, Rémi Buisson, Min Yu, Marissa Wells Madden, Joseph A LiCausi, Myriam Boukhali, Ken Tajima, Shiwei Pan, Nicola Aceto, Srinjoy Sil, Yu Zheng, Tilak Sundaresan, Toshifumi Yae, Nicole Vincent Jordan, David T Miyamoto, David T Ting, Sridhar Ramaswamy, Wilhelm Haas, Lee Zou, Daniel A Haber, Shyamala Maheswaran
TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926548/liver-transplantation-for-hepatocellular-carcinoma-current-update-on-treatment-and-allocation
#2
Leigh Anne Dageforde, Kathryn J Fowler, William C Chapman
PURPOSE OF REVIEW: This review discusses the current imaging modalities and criteria used to diagnose, and the role of liver transplantation as well as nonsurgical hepatic-directed therapies to treat hepatocellular carcinoma in the setting of chronic liver disease. RECENT FINDINGS: There has been continual evolution of guidelines, policies, and algorithms for the imaging diagnosis of hepatocellular carcinoma, particularly the Liver Imaging Reporting and Data System...
December 6, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27924021/aagatlas-1-0-a-human-autoantigen-database
#3
Dan Wang, Liuhui Yang, Ping Zhang, Joshua LaBaer, Henning Hermjakob, Dong Li, Xiaobo Yu
Autoantibodies refer to antibodies that target self-antigens, which can play pivotal roles in maintaining homeostasis, distinguishing normal from tumor tissue and trigger autoimmune diseases. In the last three decades, tremendous efforts have been devoted to elucidate the generation, evolution and functions of autoantibodies, as well as their target autoantigens. However, reports of these countless previously identified autoantigens are randomly dispersed in the literature. Here, we constructed an AAgAtlas database 1...
October 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923679/evolutionary-scalpels-for-dissecting-tumor-ecosystems
#4
Daniel I S Rosenbloom, Pablo G Camara, Tim Chu, Raul Rabadan
Amidst the growing literature on cancer genomics and intratumor heterogeneity, essential principles in evolutionary biology recur time and time again. Here we use these principles to guide the reader through major advances in cancer research, highlighting issues of "hit hard, hit early" treatment strategies, drug resistance, and metastasis. We distinguish between two frameworks for understanding heterogeneous tumors, both of which can inform treatment strategies: (1) The tumor as diverse ecosystem, a Darwinian population of sometimes-competing, sometimes-cooperating cells; (2) The tumor as tightly integrated, self-regulating organ, which may hijack developmental signals to restore functional heterogeneity after treatment...
December 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#5
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#6
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27920683/squamous-cell-carcinoma-in-african-children-with-xeroderma-pigmentosum-three-case-reports
#7
Mamadou Kaloga, Pauline Dioussé, Boubacar Ahy Diatta, Mariama Bammo, Sarah Kourouma, Almamy Diabate, Ndiaga Gueye, Haby Dione, Moussa Diallo, Bernard Marcel Diop
INTRODUCTION: Xeroderma pigmentosum is a rare autosomal recessive genetic disease. This disease predisposes patients to early-onset skin cancers, particularly squamous cell carcinoma. Here, we report 3 pediatric cases, including 2 deaths. OBSERVATION: The subjects included 2 boys and 1 girl with skin type VI. All subjects were from consanguineous marriages, and the average age was 7.6 years. The patients all had ulcerative budding tumor lesions in the cephalic region, and the mean disease duration was 18 months...
September 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/27912845/molecular-mechanisms-and-clinical-implications-of-bacterial-persistence
#8
Joran Elie Michiels, Bram Van den Bergh, Natalie Verstraeten, Jan Michiels
Any bacterial population harbors a small number of phenotypic variants that survive exposure to high concentrations of antibiotic. Importantly, these so-called 'persister cells' compromise successful antibiotic therapy of bacterial infections and are thought to contribute to the development of antibiotic resistance. Intriguingly, drug-tolerant persisters have also been identified as a factor underlying failure of chemotherapy in tumor cell populations. Recent studies have begun to unravel the complex molecular mechanisms underlying persister formation and revolve around stress responses and toxin-antitoxin modules...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#9
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911124/the-impact-of-interferon-alpha2-on-hla-genes-in-patients-with-polycythemia-vera-and-related-neoplasms
#10
Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27908264/hypoxia-and-inflammation-in-prostate-cancer-progression-cross-talk-with-androgen-and-estrogen-receptors-and-cancer-stem-cells
#11
Matteo A Russo, Linda Ravenna, Laura Pellegrini, Elisa Petrangeli, Luisa Salvatori, Thea Magrone, Massimo Fini, Marco Tafani
Tumors are complex tissues in which transformed cells communicate with the surrounding microenvironment and evolve traits promoting their own survival and malignancy. Hypoxia and inflammation are constant characteristics of prostate tumor microenvironment influencing both cancer stem cells and differentiated tumor cells. HIFs and NF-kB are the key regulators of the transcriptional response to hypoxic and inflammatory stresses, respectively, and a crosstalk between HIFs and NF-kB pathways has been widely documented...
November 30, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/27904775/disease-evolution-and-heterogeneity-in-bilateral-breast-cancer
#12
Elena Fountzilas, Vassiliki Kotoula, Flora Zagouri, Eleni Giannoulatou, George Kouvatseas, George Pentheroudakis, Triantafyllia Koletsa, Mattheos Bobos, Kyriaki Papadopoulou, Epaminontas Samantas, Efterpi Demiri, Spyros Miliaras, Christos Christodoulou, Sofia Chrisafi, Evangelia Razis, Florentia Fostira, Dimitrios Pectasides, George Zografos, George Fountzilas
Bilateral breast cancers (BBC) are currently treated as independent tumors arising in the same patient. Herein, we investigated whether BBC indeed evolve independently at the genomic level. We examined paired targeted next generation sequencing genotypes from 155 paraffin tumors corresponding to 76 BBC patients (75 women and one man; 52 concurrent and 24 metachronous), for coding mutations (amino acid changing, minor allele frequency <0.1%) and single nucleotide polymorphism (SNP) zygosity. Germline genotypes were available for 29 patients...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903126/potential-evolution-of-neurosurgical-treatment-paradigms-for-craniopharyngioma-based-on-genomic-and-transcriptomic-characteristics
#13
Leslie C Robinson, Sandro Santagata, Todd C Hankinson
The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27901326/tuberculuma-sellae-meningiomas-a-systematic-review-of-transcranial-approaches-in-the-endoscopic-era
#14
Mazda Turel, Georgios Tsermoulas, Abdulmounem Yasssin-Kassab, Deven Reddy, Hugo Andrade-Barazarte, Lior Gonen, Gelareh Zadeh, Fred Gentili
INTRODUCTION: With the advent of skull base endoscopy, tuberculum sellae meningiomas (TSMs) are currently operated both from the traditional transcranial (TC) route as well as the extended endonasal endoscopic trasnssphenoidal approach (EETS). The aim of this study was to conduct a systematic review of TSMs excised via the TC route in the modern era when the EETS excision is gaining popularity. EVIDENCE ACQUISITION: We performed a systematic review in the medical literature following the PRISMA guidelines...
November 30, 2016: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/27898034/emerging-non-canonical-functions-and-regulation-by-p53-p53-and-stemness
#15
REVIEW
David J Olivos, Lindsey D Mayo
Since its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53's functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27895661/the-genome-conformation-as-an-integrator-of-multi-omic-data-the-example-of-damage-spreading-in-cancer
#16
Fabio Tordini, Marco Aldinucci, Luciano Milanesi, Pietro Liò, Ivan Merelli
Publicly available multi-omic databases, in particular if associated with medical annotations, are rich resources with the potential to lead a rapid transition from high-throughput molecular biology experiments to better clinical outcomes for patients. In this work, we propose a model for multi-omic data integration (i.e., genetic variations, gene expression, genome conformation, and epigenetic patterns), which exploits a multi-layer network approach to analyse, visualize, and obtain insights from such biological information, in order to use achieved results at a macroscopic level...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27893374/differential-evolution-optimization-of-the-sar-distribution-for-head-and-neck-hyperthermia
#17
Grazia Cappiello, Brian Mc Ginley, Muhammad Adnan Elahi, Tomas Drizdal, Margarethus M Paulides, Martin Glavin, Martin O'Halloran, Edward Jones
Hyperthermia is an emerging cancer treatment modality which involves applying heat to the malignant tumor. The heating can be delivered using electromagnetic (EM) energy, mostly in the radiofrequency (RF) or microwave range. Accurate patient-specific hyperthermia treatment planning (HTP) is essential for effective and safe treatments, in particular for deep and loco-regional hyperthermia. An important aspect of HTP is the ability to focus microwave energy into the tumor and reduce the occurrence of hot spots in healthy tissue...
November 14, 2016: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/27891175/multidetector-computer-tomography-in-the-pancreatic-adenocarcinoma-assessment-an-update
#18
REVIEW
Vincenza Granata, Roberta Fusco, Orlando Catalano, Sergio Venanzio Setola, Elisabetta de Lutio di Castelguidone, Mauro Piccirillo, Raffaele Palaia, Roberto Grassi, Francesco Granata, Francesco Izzo, Antonella Petrillo
Ductal adenocarcinoma of the pancreas is one of the most aggressive forms of cancer, with only a minority of cases being resectable at the moment of their diagnosis. The accurate detection and characterization of pancreatic carcinoma is very important for patient management. Multidetector-row computed tomography (MDCT) has become the cross-sectional modality of choice in the diagnosis, staging, treatment planning, and follow-up of patients with pancreatic tumors. However, approximately 11% of ductal adenocarcinomas still remain undetected at MDCT because of the lack of attenuation gradient between the lesion and the adjacent pancreatic parenchyma...
2016: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/27888671/sclerosing-polycystic-adenosis-of-the-parotid-gland-a-systematic-review-and-report-of-2-new-cases
#19
Carlos A Espinosa, Laura Rua, Héctor E Torres, Álvaro Fernández Del Valle, Rui P Fernandes, Juan C Devicente
PURPOSE: We sought to evaluate clinical-epidemiologic aspects, pathologic characteristics, and treatment of sclerosing polycystic adenosis (SPA) of the parotid gland and to report 2 new cases. MATERIALS AND METHODS: We conducted a systematic review following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies published in or before June 2016. The inclusion criteria were as follows: final diagnosis of SPA affecting the parotid gland and articles published in Spanish or English...
November 2, 2016: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/27888226/single-cell-sequencing-maps-gene-expression-to-mutational-phylogenies-in-pdgf-and-egf-driven-gliomas
#20
Sören Müller, Siyuan John Liu, Elizabeth Di Lullo, Martina Malatesta, Alex A Pollen, Tomasz J Nowakowski, Gary Kohanbash, Manish Aghi, Arnold R Kriegstein, Daniel A Lim, Aaron Diaz
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in GBM However, clinical trials of tyrosine-kinase inhibitors have shown disappointing efficacy, in part due to intra-tumor heterogeneity. To assess the effect of clonal heterogeneity on gene expression, we derived an approach to map single-cell expression profiles to sequentially acquired mutations identified from exome sequencing...
November 25, 2016: Molecular Systems Biology
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