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https://www.readbyqxmd.com/read/28640705/genomic-analysis-of-childhood-brain-tumors-methods-for-genome-wide-discovery-and-precision-medicine-become-mainstream
#1
Stephen C Mack, Paul A Northcott
Recent breakthroughs in next-generation sequencing technology and complementary genomic platforms have transformed our capacity to interrogate the molecular landscapes of human cancers, including childhood brain tumors. Numerous high-throughput genomic studies have been reported for the major histologic brain tumor entities diagnosed in children, including interrogations at the level of the genome, epigenome, and transcriptome, many of which have yielded essential new insights into disease biology. The nature of these discoveries has been largely platform dependent, exemplifying the usefulness of applying different genomic and computational strategies, or integrative approaches, to address specific biologic and/or clinical questions...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640696/insights-from-molecular-profiling-of-adult-glioma
#2
Phedias Diamandis, Kenneth D Aldape
The comprehensive molecular profiling of cancer has resulted in new insights into the biology and classification of numerous tumor types. In the case of primary brain tumors that commonly affect adults, an emerging set of disease-defining biomarker sets is reshaping existing diagnostic entities that had previously been defined on the basis of their microscopic appearance. Substantial progress has been made in this regard for common primary brain tumors in adults, especially diffuse gliomas, where large-scale profiling efforts have led to the incorporation of highly prevalent molecular alterations that promote a biologically based classification as an adjunct to the traditional histopathologic approach...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640663/glycosylation-profile-and-biological-activity-of-remicade%C3%A2-compared-with-flixabi%C3%A2-and-remsima%C3%A2
#3
Changsoo Lee, Min Jeong, JongAh Joanne Lee, Saebom Seo, Sung Chun Cho, Wei Zhang, Orlando Jaquez
As biosimilars enter the market, comparisons of product quality are needed. Manufacturing differences may lead to differences in critical quality attributes, which affect efficacy. Therefore, critical quality attributes (structure and biological activity) of Remicade® and of 2 biosimilar products (Flixabi®/Renflexis® and Remsima®/Inflectra®) were determined. We assessed binding to tumor necrosis factor in a fluorescence competitive binding assay; potency in a luciferase reporter gene assay; percentages of galactosylated glycan, afucose plus high mannosylated glycans, and charged glycan; FcγRIIIa (CD16) binding (assessed by 3 methods); and antibody-dependent cell-mediated cytotoxicity (ADCC) in the NK92-CD16a cell line and in peripheral blood mononuclear cells (PBMC)...
June 22, 2017: MAbs
https://www.readbyqxmd.com/read/28637015/differential-metabonomic-profiles-of-primary-hepatocellular-carcinoma-tumors-from-alcoholic-liver-disease-hbv-infected-and-hcv-infected-cirrhotic-patients
#4
Ding Cao, Can Cai, Mingxin Ye, Junhua Gong, Menghao Wang, Jinzheng Li, Jianping Gong
Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC tumors from the three groups...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637013/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#5
Renato José Silva-Oliveira, Matias Melendez, Olga Martinho, Maicon F Zanon, Luciano de Souza Viana, André Lopes Carvalho, Rui Manuel Reis
Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637008/cytotoxic-profiling-of-artesunic-and-betulinic-acids-and-their-synthetic-hybrid-compound-on-neurons-and-gliomas
#6
Annemarie Ackermann, Aysun Çapcı Karagöz, Ali Ghoochani, Michael Buchfelder, Ilker Eyüpoglu, Svetlana B Tsogoeva, Nicolai Savaskan
Gliomas are brain-born tumors with devastating impact on their brain microenvironment. Novel approaches employ multiple combinations of chemical compounds in synthetic hybrid molecules to target malignant tumors. Here, we report on the chemical hybridization approach exemplified by artesunic acid (ARTA) and naturally occurring triterpene betulinic acid (BETA). Artemisinin derived semisynthetic compound artesunic acid (ARTA) and naturally occurring triterpene BETA were used to synthetically couple to the hybrid compound termed 212A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636998/physiologically-based-pharmacokinetic-modeling-for-predicting-irinotecan-exposure-in-human-body
#7
Yingfang Fan, Najia Mansoor, Tasneem Ahmad, Rafeeq Alam Khan, Martin Czejka, Syed Sharib, Dong-Hua Yang, Mansoor Ahmed
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636973/amide-to-triazole-switch-vs-in-vivo-nep-inhibition-approaches-to-promote-radiopeptide-targeting-of-grpr-positive-tumors
#8
Theodosia Maina, Aikaterini Kaloudi, Ibai E Valverde, Thomas L Mindt, Berthold A Nock
INTRODUCTION: Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG4-[Nle(14)]BBN(7-14) (1) was reported to improve the in vitro stability of resulting (177)Lu-radioligands...
June 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28636877/lectin-cgl-from-the-sea-mussel-crenomytilus-grayanus-induces-burkitt-s-lymphoma-cells-death-via-interaction-with-surface-glycan
#9
Oleg Chernikov, Alexandra Kuzmich, Irina Chikalovets, Valentina Molchanova, Kuo-Feng Hua
Marine organisms are rich sources of lectins. Lectins are able to bind specifically and reversibly to different types of carbohydrates or glycoproteins. The present study reports the evaluation of glycan binding profile and anti-tumor potential of lectin CGL from the sea mussel Crenomytilus grayanus. Glycan array assay revealed that CGL was able to bind both α and β anomer of galactose, but interaction with the αGal-terminated glycans was stronger. Analysis of most common glycan motifs for CGL showed high affinity to Galα1-4Galβ1-4GlcNAc motif similar to globotriose structure (Gb3: Galα1-4Galβ1-4Glc), the epitope of globotriaosylceramide...
June 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28636851/first-line-nivolumab-in-stage-iv-or-recurrent-non-small-cell-lung-cancer
#10
COMMENT
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski
BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. METHODS: We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles)...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636540/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#11
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#12
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635565/prostate-cancer-stem-cells-from-theory-to-practice
#13
Jan Adamowicz, Katayoon Pakravan, Babak Bakhshinejad, Tomasz Drewa, Sadegh Babashah
None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease...
February 7, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28635560/sorafenib-in-japanese-patients-with-locally-advanced-or-metastatic-medullary-thyroid-carcinoma-and-anaplastic-thyroid-carcinoma
#14
Yasuhiro Ito, Naoyoshi Onoda, Ken-Ichi Ito, Iwao Sugitani, Shunji Takahashi, Iku Yamaguchi, Koki Kabu, Katsuya Tsukada
BACKGROUND: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan even though vandetanib for MTC, and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). We conducted an uncontrolled, open-label, multicenter, single-arm, phase 2 clinical study to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC...
June 21, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#15
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28635404/safety-and-efficacy-of-hepasphere-50-100%C3%A2-%C3%AE-m-in-the-treatment-of-hepatocellular-carcinoma
#16
Charles Edouard Zurstrassen, Luiz Paulo De Oliveira Gireli, Chiang Jeng Tyng, Almir Galvão Vieira Bitencourt, Marcos Duarte Guimarães, Paula Nicole Vieira Barbosa, Aline Cristine Barbosa Santos Cavalcante, João Paulo Matushita Junior, Mauricio Kauark Amoedo, Felipe Jose Coimbra, Rogério Camargo Pinheiro Alves, Rubens Chojniak
AIM: To evaluate the effects of HepaSphere 50-100 μm (Merit Medical) as a doxorubicin carrier and embolization agent for the treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: A prospective analysis of 18 patients recruited from a national cancer center was conducted. This analysis evaluated the efficacy and safety of HepaSphere, as expressed by the treatment response rate (measured by the modified Response Evaluation Criteria in Solid Tumors, mRECIST) and by the prevalence of treatment-related adverse events, respectively...
February 14, 2017: Minimally Invasive Therapy & Allied Technologies: MITAT
https://www.readbyqxmd.com/read/28635333/molecular-biomarkers-to-guide-precision-medicine-in-localized-prostate-cancer
#17
Minke Smits, Niven Mehra, Michiel Sedelaar, Winald Gerritsen, Jack A Schalken
Major advances through tumor profiling technologies, that include next-generation sequencing, epigenetic, proteomic and transcriptomic methods, have been made in primary prostate cancer, providing novel biomarkers that may guide precision medicine in the near future. Areas covered: The authors provided an overview of novel molecular biomarkers in tissue, blood and urine that may be used as clinical tools to assess prognosis, improve selection criteria for active surveillance programs, and detect disease relapse early in localized prostate cancer...
June 21, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28634515/transarterial-chemoembolization-using-40-%C3%A2%C2%B5m-drug-eluting-beads-for-hepatocellular-carcinoma
#18
Giorgio Greco, Tommaso Cascella, Antonio Facciorusso, Roberto Nani, Rodolfo Lanocita, Carlo Morosi, Marta Vaiani, Giuseppina Calareso, Francesca G Greco, Antonio Ragnanese, Marco A Bongini, Alfonso V Marchianò, Vincenzo Mazzaferro, Carlo Spreafico
AIM: To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment. METHODS: Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging...
May 28, 2017: World Journal of Radiology
https://www.readbyqxmd.com/read/28634418/long-noncoding-rnas-as-biomarkers-in-cancer
#19
REVIEW
Luka Bolha, Metka Ravnik-Glavač, Damjan Glavač
Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, intracellular trafficking, and chromosome remodeling. Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis. In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer...
2017: Disease Markers
https://www.readbyqxmd.com/read/28634396/epigenetic-silencing-of-downstream-genes-mediated-by-tandem-orientation-in-lung-cancer
#20
Steffen Kiehl, Tobias Zimmermann, Rajkumar Savai, Soni S Pullamsetti, Werner Seeger, Marek Bartkuhn, Reinhard H Dammann
Epigenetic deregulation is of importance in tumorigenesis. In particular CpG islands (CGI), are frequently hypermethylated. Here, genome-wide DNA-methylation profiles of 480,000 CpGs in lung cancer cells were generated. It was observed that intra- and intergenic CGI exhibited higher methylation compared to normal cells. The functional annotation of hypermethylated CGI revealed that the hypermethylation was associated with homeobox domain genes and targets marked by repressive histone modifications. The strongest methylation variation was observed in transitional areas of CGI, termed shores...
June 20, 2017: Scientific Reports
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