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https://www.readbyqxmd.com/read/28728166/whole-genome-sequencing-revealed-novel-prognostic-biomarkers-and-promising-targets-for-therapy-of-ovarian-clear-cell-carcinoma
#1
Hiroaki Itamochi, Tetsuro Oishi, Nao Oumi, Satoshi Takeuchi, Kosuke Yoshihara, Mikio Mikami, Nobuo Yaegashi, Yasuhisa Terao, Kazuhiro Takehara, Kimio Ushijima, Hidemichi Watari, Daisuke Aoki, Tadashi Kimura, Toshiaki Nakamura, Yoshihito Yokoyama, Junzo Kigawa, Toru Sugiyama
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours. METHODS: Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols. RESULTS: Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively...
July 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28727999/drug-ion-co-delivery-multi-functional-nanocarrier-to-regenerate-infected-tissue-defect
#2
Jung-Hwan Lee, Ahmed El-Fiqi, Nandin Mandakhbayar, Hae-Hyoung Lee, Hae-Won Kim
Regeneration of infected tissues is a globally challenging issue in medicine and dentistry. Common clinical therapies involving a complete removal of infected areas together with a treatment of antimicrobial drugs are often suboptimal. Biomaterials with anti-bacterial and pro-regenerative potential can offer a solution to this. Here we design a novel nanocarrier based on a mesoporous silicate-calcium glass by doping with Ag ions and simultaneously loading antimicrobial drugs onto mesopores. The nanocarriers could controllably release multiple ions (silver, calcium, and silicate) and drugs (tetracycline or chlorohexidine) to levels therapeutically relevant, and effectively internalize to human dental stem cells (∼90%) with excellent viability, ultimately stimulating odontogenic differentiation...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28727865/proton-beam-radiotherapy-and-concurrent-chemotherapy-for-unresectable-stage-iii-non-small-cell-lung-cancer-final-results-of-a-phase-2-study
#3
Joe Y Chang, Vivek Verma, Ming Li, Wencheng Zhang, Ritsuko Komaki, Charles Lu, Pamela K Allen, Zhongxing Liao, James Welsh, Steven H Lin, Daniel Gomez, Melenda Jeter, Michael O'Reilly, Ronald X Zhu, Xiaodong Zhang, Heng Li, Radhe Mohan, John V Heymach, Ara A Vaporciyan, Stephen Hahn, James D Cox
Importance: Proton beam radiotherapy (PBT) has the potential to reduce toxic effects in the definitive management of locally advanced non-small-cell lung cancer (NSCLC), but long-term prospective data are lacking. Objective: To report the final (5-year) results of a prospective study evaluating concurrent chemotherapy and high-dose PBT to treat unresectable stage III NSCLC. Design, Setting, and Participants: In this open-label, single-group assignment study, with median follow-up of 27...
July 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28727782/detecting-expression-of-5t4-in-ctcs-and-tumor-samples-from-nsclc-patients
#4
Steven R Pirie-Shepherd, Cory Painter, Pamela Whalen, Pamela Vizcarra, Marc Roy, Jesse Qian, Tania Franks, Tim Coskran, Jon Golas, Shibing Deng, Wenyan Zhong, Eric Tucker, Dena Marrinucci, Hans-Peter Gerber, Eric L Powell
The fetal oncogene 5T4 is a cell surface protein, with overexpression observed in a variety of cancers as compared to normal adult tissue. The ability to select patients with tumors that express high levels of 5T4 may enrich a clinical trial cohort with patients most likely to respond to 5T4 targeted therapy. To that end, we developed assays to measure 5T4 in both tumors and in circulating tumor cells (CTCs). We identified the presence of 5T4 in both adenocarcinoma and squamous cell carcinoma of lung, in all clinical stages and grades of disease...
2017: PloS One
https://www.readbyqxmd.com/read/28727518/therapeutic-and-prognostic-implications-of-braf-v600e-in-pediatric-low-grade-gliomas
#5
Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara McKeown, Jim Loukides, Ofelia Cruz, Carmen de Torres, Cheng-Ying Ho, Roger J Packer, Ruth Tatevossian, Ibrahim Qaddoumi, Julie H Harreld, James D Dalton, Jean Mulcahy-Levy, Nicholas Foreman, Matthias A Karajannis, Shiyang Wang, Matija Snuderl, Amulya Nageswara Rao, Caterina Giannini, Mark Kieran, Keith L Ligon, Maria Luisa Garre, Paolo Nozza, Samantha Mascelli, Alessandro Raso, Sabine Mueller, Theodore Nicolaides, Karen Silva, Romain Perbet, Alexandre Vasiljevic, Cécile Faure Conter, Didier Frappaz, Sarah Leary, Courtney Crane, Aden Chan, Ho-Keung Ng, Zhi-Feng Shi, Ying Mao, Elizabeth Finch, David Eisenstat, Bev Wilson, Anne Sophie Carret, Peter Hauser, David Sumerauer, Lenka Krskova, Valerie Larouche, Adam Fleming, Shayna Zelcer, Nada Jabado, James T Rutka, Peter Dirks, Michael D Taylor, Shiyi Chen, Ute Bartels, Annie Huang, David W Ellison, Eric Bouffet, Cynthia Hawkins, Uri Tabori
Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180)...
July 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28727221/scar-formation-following-excisional-and-burn-injuries-in-a-red-duroc-pig-model
#6
Britani N Blackstone, Jayne Y Kim, Kevin L McFarland, Chandan K Sen, Dorothy M Supp, J Kevin Bailey, Heather M Powell
Scar research is challenging because rodents do not naturally form excessive scars, and burn depth, size, and location cannot be controlled in human longitudinal studies. The female, red Duroc pig model has been shown to form robust scars with biological and anatomical similarities to human hypertrophic scars. To more closely mimic the mode of injury, recreate the complex chemical milieu of the burn wound environment and enhance scar development, an animal model of excessive burn-induced scarring was developed and compared with the more commonly used model, which involves excisional wounds created via dermatome...
July 20, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28726821/the-whole-genome-landscape-of-medulloblastoma-subtypes
#7
Paul A Northcott, Ivo Buchhalter, A Sorana Morrissy, Volker Hovestadt, Joachim Weischenfeldt, Tobias Ehrenberger, Susanne Gröbner, Maia Segura-Wang, Thomas Zichner, Vasilisa A Rudneva, Hans-Jörg Warnatz, Nikos Sidiropoulos, Aaron H Phillips, Steven Schumacher, Kortine Kleinheinz, Sebastian M Waszak, Serap Erkek, David T W Jones, Barbara C Worst, Marcel Kool, Marc Zapatka, Natalie Jäger, Lukas Chavez, Barbara Hutter, Matthias Bieg, Nagarajan Paramasivam, Michael Heinold, Zuguang Gu, Naveed Ishaque, Christina Jäger-Schmidt, Charles D Imbusch, Alke Jugold, Daniel Hübschmann, Thomas Risch, Vyacheslav Amstislavskiy, Francisco German Rodriguez Gonzalez, Ursula D Weber, Stephan Wolf, Giles W Robinson, Xin Zhou, Gang Wu, David Finkelstein, Yanling Liu, Florence M G Cavalli, Betty Luu, Vijay Ramaswamy, Xiaochong Wu, Jan Koster, Marina Ryzhova, Yoon-Jae Cho, Scott L Pomeroy, Christel Herold-Mende, Martin Schuhmann, Martin Ebinger, Linda M Liau, Jaume Mora, Roger E McLendon, Nada Jabado, Toshihiro Kumabe, Eric Chuah, Yussanne Ma, Richard A Moore, Andrew J Mungall, Karen L Mungall, Nina Thiessen, Kane Tse, Tina Wong, Steven J M Jones, Olaf Witt, Till Milde, Andreas Von Deimling, David Capper, Andrey Korshunov, Marie-Laure Yaspo, Richard Kriwacki, Amar Gajjar, Jinghui Zhang, Rameen Beroukhim, Ernest Fraenkel, Jan O Korbel, Benedikt Brors, Matthias Schlesner, Roland Eils, Marco A Marra, Stefan M Pfister, Michael D Taylor, Peter Lichter
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28726797/multiple-myeloma
#8
REVIEW
Shaji K Kumar, Vincent Rajkumar, Robert A Kyle, Mark van Duin, Pieter Sonneveld, María-Victoria Mateos, Francesca Gay, Kenneth C Anderson
Multiple myeloma is a malignancy of terminally differentiated plasma cells, and patients typically present with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine. The diagnosis of multiple myeloma is made when clear end-organ damage attributable to the plasma cell proliferative disorder or when findings that suggest a high likelihood of their development are present. Distinguishing symptomatic multiple myeloma that requires treatment from the precursor stages of monoclonal gammopathy of undetermined significance and smouldering multiple myeloma is important, as observation is the standard for those conditions...
July 20, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28726770/a-model-for-the-regulation-of-follicular-dendritic-cells-predicts-invariant-reciprocal-time-decay-of-post-vaccine-antibody-response
#9
Anthony Almudevar
Follicular dendritic cells (FDC) play a crucial role in the regulation of humoral immunity. They are believed to be responsible for long-term persistence of antibody, due to their role in antibody response induction and their ability to retain antigen in immunogenic form for long periods. In this article, a regulatory control model is proposed which links persistence of humoral immunity with cellular processes associated with FDCs. The argument is comprised of three elements. The first is a literature review of population-level studies of post-vaccination antibody persistence...
July 20, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28726731/the-use-of-imaging-in-the-prediction-and-assessment-of-cancer-treatment-toxicity
#10
REVIEW
Hossein Jadvar
Multimodal imaging is commonly used in the management of patients with cancer. Imaging plays pivotal roles in the diagnosis, initial staging, treatment response assessment, restaging after treatment and the prognosis of many cancers. Indeed, it is difficult to imagine modern precision cancer care without the use of multimodal molecular imaging, which is advancing at a rapid pace with innovative developments in imaging sciences and an improved understanding of the complex biology of cancer. Cancer therapy often leads to undesirable toxicity, which can range from an asymptomatic subclinical state to severe end organ damage and even death...
July 20, 2017: Diagnostics
https://www.readbyqxmd.com/read/28726495/use-of-adeno-associated-virus-vector-for-cardiac-gene-delivery-in-large-animal-surgical-models-of-heart-failure
#11
Michael G Katz, Anthony S Fargnoli, Thomas Weber, Roger Hajjar, Charles Bridges
The advancement of gene-therapy-based approaches to treat heart disease represents a need for clinically-relevant animal models with characteristics equivalent to human pathologies. Rodent models of cardiac disease do not precisely reproduce heart failure phenotype and molecular defects. This has motivated researchers to use large animals whose heart size and physiological processes more similar and comparable to those of humans. Today, adeno-associated viruses (AAV)-based vectors are undoubtedly among the most promising DNA delivery vehicles...
July 20, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28726387/aryl-substituted-ruthenium-ii-complexes-a-strategy-for-enhanced-photocleavage-and-efficient-dna-binding
#12
Felipe Diógenes Abreu, Tercio de F Paulo, Marcelo H Gehlen, Rômulo A Ando, Luiz G F Lopes, Ana Cláudia S Gondim, Mayron A Vasconcelos, Edson H Teixeira, Eduardo Henrique Silva Sousa, Idalina Maria Moreira de Carvalho
Ruthenium polypyridine complexes have shown promise as agents for photodynamic therapy (PDT) and tools for molecular biology (chromophore-assisted light inactivation). To accomplish these tasks, it is important to have at least target selectivity and great reactive oxygen species (ROS) photogeneration: two properties that are not easily found in the same molecule. To prepare such new agents, we synthesized two new ruthenium complexes that combine an efficient DNA binding moiety (dppz ligand) together with naphthyl-modified (1) and anthracenyl-modified (2) bipyridine as a strong ROS generator bound to a ruthenium complex...
July 20, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28725977/the-effect-of-vitamin-d-and-calcium-supplementation-in-pediatric-steroid-sensitive-nephrotic-syndrome
#13
Sushmita Banerjee, Surupa Basu, Ananda Sen, Jayati Sengupta
BACKGROUND: Low serum levels of total 25-hydroxycholecalciferol (25(OH)D) occur in nephrotic syndrome (NS). We aimed to assess the effects of vitamin D3 and calcium supplementation on 25(OH)D levels, bone mineralization, and NS relapse rate in children with steroid-sensitive NS. METHODS: A randomized controlled trial (RCT) was performed in children with steroid-sensitive NS. The treatment group received vitamin D3 (60,000 IU orally, weekly for 4 weeks) and calcium supplements (500 to 1,000 mg/day for 3 months) after achieving NS remission...
July 19, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28725955/biologics-in-juvenile-idiopathic-arthritis-a-narrative-review
#14
REVIEW
Federica Vanoni, Francesca Minoia, Clara Malattia
In the past years, pediatric rheumatology has seen a revolution in the treatments for rheumatic diseases, particularly juvenile idiopathic arthritis. Even if nonsteroidal anti-inflammatory drugs (NSAID), intra-articular corticosteroids (IAC) injections, and methotrexate remain the mainstay of the treatment for JIA patients, in aggressive disease, these treatments may be not sufficient to reach disease remission and to prevent long-term disability. Comprehension of immunological mechanisms involved in the pathogenesis of the diseases allowed to conceive new drugs targeting specific steps of the immune response...
July 20, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28725635/implications-of-micrornas-in-oncolytic-virotherapy
#15
REVIEW
Xavier Bofill-De Ros, Maria Rovira-Rigau, Cristina Fillat
MicroRNAs (miRNAs) are an abundant class of small non-coding RNA molecules (~22 nt) that can repress gene expression. Deregulation of certain miRNAs is widely recognized as a robust biomarker for many neoplasms, as well as an important player in tumorigenesis and the establishment of tumoral microenvironments. The downregulation of specific miRNAs in tumors has been exploited as a mechanism to provide selectivity to oncolytic viruses or gene-based therapies. miRNA response elements recognizing miRNAs expressed in specific tissues, but downregulated in tumors, have been inserted into the 3'UTR of viral genes to promote the degradation of these viral mRNAs in healthy tissue, but not in tumor cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#16
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28725583/positron-emission-tomography-pet-in-primary-prostate-cancer-staging-and-risk-assessment
#17
REVIEW
Sandra Bednarova, Maria L Lindenberg, Maria Vinsensia, Chiara Zuiani, Peter L Choyke, Baris Turkbey
Prostate cancer (PCa) is one of the few neoplasms that are not well served by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). As a result, a number of PET tracers have been developed to target particular biological features of PCa. Such agents can be used for diagnosis, staging, identification of biochemical recurrence (BCR) and evaluation of metastatic disease. Here, we focus on primary disease and local staging. To date, magnetic resonance imaging (MRI) has proven superior to PET in the imaging of primary PCa...
June 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28725570/enzyme-activities-of-%C3%AE-glucosidase-in-japanese-neonates-with-pseudodeficiency-alleles
#18
Ryuichi Mashima, Torayuki Okuyama
Lysosomal storage disorders (LSDs) are caused by defective enzyme activities in lysosomes, characterized by the accumulation of sphingolipids, glycolipids, oligosaccharides, mucopolysaccharides, the oxidation products of cholesterol, and other biological substances. A growing number of clinical studies have suggested the enhanced efficacy of existing therapies, including enzyme replacement therapy, which is effective when it is initiated during the presymptomatic period. Thus, the identification of disease-affected individuals by newborn screening has been considered an effective platform...
September 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28725558/temperature-dependent-optoacoustic-response-and-transient-through-zero-gr%C3%A3-neisen-parameter-in-optically-contrasted-media
#19
Elena Petrova, Anton Liopo, Alexander A Oraevsky, Sergey A Ermilov
Non-invasive optoacoustic mapping of temperature in tissues with low blood content can be enabled by administering external contrast agents. Some important clinical applications of such approach include temperature mapping during thermal therapies in a prostate or a mammary gland. However, the technique would require a calibration that establishes functional relationship between the measured normalized optoacoustic response and local tissue temperature. In this work, we investigate how a key calibration parameter - the temperature of zero optoacoustic response (T0 ) - behaves in different environments simulating biological tissues augmented with either dissolved or particulate (nanoparticles) contrast agents...
September 2017: Photoacoustics
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#20
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
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